coenzyme-q10 and Disease-Models--Animal

Mitochondrial function is closely linked to numerous aspects of eye health. Imbalance between the creation of energy and the development of reactive oxygen species (ROS) seems to be the cause of the development of mitochondrial dysfunctions. As a result of this energy deficit, the level of oxidative stress in the eye tissues increases, leading to numerous ophthalmic impairments. It is important to distinguish between primary mitochondrial eye diseases and secondary mitochondrial changes. Primary mitochondrial eye diseases, for example Leber's hereditary optic atrophy (LHON), retinitis pigmentosa and chronic progressive external ophthalmoplegia are caused by direct damage to mitochondrial function induced by defective genes, either located on mitochondrial DNA (mtDNA) or the DNA of the nucleus (nDNA). In contrast, secondary mitochondrial dysfunctions are caused by environmental factors. In recent years, there has been growing evidence that mitochondrial dysfunctions play an important role in many common eye diseases, such as glaucoma, dry eye, diabetic retinopathy, cataract and age-related macular degeneration (AMD). This article summarises current knowledge of mitochondrial dysfunctions and the role of coenzyme Q10 (CoQ10) as a possible treatment option - with a special focus on glaucoma.. Die mitochondriale Funktion ist mit zahlreichen Aspekten der Gesundheit des Auges eng verknüpft. Ursächlich für mitochondriale Dysfunktionen scheint ein Ungleichgewicht zwischen der Bildung von Energie und der Menge an freien Radikalen zu sein. Dadurch kommt es neben einem Energiemangel zu einer erhöhten oxidativen Belastung der betroffenen Augengewebe mit der Folge einer Vielzahl von ophthalmologischen Beeinträchtigungen. Dabei wird zwischen primären und sekundären mitochondrialen Augenerkrankungen unterschieden. Primäre mitochondriale Erkrankungen wie bspw. die Leberʼsche hereditäre Optikusatrophie (LHON), die Retinitis pigmentosa und die chronisch progressive externe Ophthalmoplegie sind die Folge von direkten Schädigungen der mitochondrialen Funktion durch defekte Gene auf der mitochondrialen DNA (mtDNA) oder auf der nukleären DNA (nDNA). Demgegenüber sind sekundäre mitochondriale Dysfunktionen vor allem auf Umwelteinflüsse zurückzuführen. In jüngster Zeit häufen sich Hinweise darauf, dass auch mitochondriale Dysfunktionen bei vielen häufig auftretenden Augenerkrankungen wie dem Glaukom, dem „Trockenen Auge“, der diabetischen Retinopathie, der Katarakt und der altersabhängigen Makuladegeneration (AMD) eine wichtige Rolle spielen. Dieser Beitrag fasst den derzeitigen Kenntnisstand zu mitochondrialen Dysfunktionen und zur Rolle von Coenzym Q10 (CoQ10) als mögliche Therapieoption beim Glaukom zusammen.

Topics: Animals; Biological Availability; Diagnosis, Differential; Disease Models, Animal; Electron Transport; Energy Metabolism; Eye; Free Radicals; Glaucoma; Humans; Microscopy, Electron; Mitochondrial Diseases; Ophthalmic Solutions; Reactive Oxygen Species; Risk Factors; Ubiquinone

Mitochondrial dysfunction characterized by impaired bioenergetics, oxidative stress and aldehydic load is a hallmark of heart failure. Recently, different research groups have provided evidence that selective activation of mitochondrial detoxifying systems that counteract excessive accumulation of ROS, RNS and reactive aldehydes is sufficient to stop cardiac degeneration upon chronic stress, such as heart failure. Therefore, pharmacological and non-pharmacological approaches targeting mitochondria detoxification may play a critical role in the prevention or treatment of heart failure. In this review we discuss the most recent findings on the central role of mitochondrial dysfunction, oxidative stress and aldehydic load in heart failure, highlighting the most recent preclinical and clinical studies using mitochondria-targeted molecules and exercise training as effective tools against heart failure.

Topics: Aldehydes; Animals; Antioxidants; Biomimetic Materials; Cardiotonic Agents; Clinical Trials as Topic; Disease Models, Animal; Drug Evaluation, Preclinical; Energy Metabolism; Exercise; Heart Failure; Humans; Malondialdehyde; Mitochondria, Heart; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species; Superoxide Dismutase; Ubiquinone

Statins inhibit hydroxymethylglutaryl-coenzyme A reductase, decrease plasma low-density lipoprotein cholesterol and reduce cardiovascular morbidity and mortality. They can also exert adverse effects, mostly affecting skeletal muscle, ranging from mild myalgia to rhabdomyolysis.. Based on a PubMed search until December 2014, this review summarizes studies on statin effects on muscle mitochondrial morphology and function in the context of myopathy.. Possible mechanisms of statin-induced myopathy include lower cholesterol synthesis and production of prenylated proteins, reduced dolichols and increased atrogin-1 expression. Statin-treated patients frequently feature decreased muscle coenzyme Q10 (CoQ10) contents, suggesting that statins might impair mitochondrial function. In cell cultures, statins diminish muscle oxygen consumption, promote mitochondrial permeability transient pore opening and generate apoptotic proteins. Animal models confirm the statin-induced decrease in muscle CoQ10, but reveal no changes in mitochondrial enzyme activities. Human studies yield contradictory results, with decreased CoQ10, elevated lipids, decreased enzyme activities in muscle and impaired maximal oxygen uptake in several but not all studies. Some patients are susceptible to statin-induced myopathy due to variations in genes encoding proteins involved in statin uptake and biotransformation such as the solute carrier organic anion transporter family member 1B1 (SLCO1B1) or cytochrome P450 (CYP2D6, CYP3A4, CYP3A5). Carriers for carnitine palmitoyltransferase II deficiency and McArdle disease also present with higher prevalence of statin-induced myopathy.. Despite the widespread use of statins, the pathogenesis of statin-induced myopathy remains unclear, requiring prospective randomized controlled trials with intensive phenotyping also for identifying strategies for its risk assessment, prevention and treatment.

Topics: Animals; Cell Line; Disease Models, Animal; Energy Metabolism; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mitochondria, Muscle; Muscle, Skeletal; Muscular Diseases; Rabbits; Rats; Risk Factors; Ubiquinone

Huntington's disease (HD) is a prototypical dominantly inherited neurodegenerative disorder characterized by progressive cognitive deterioration, psychiatric disturbances, and a movement disorder. The genetic cause of the illness is a CAG repeat expansion in the huntingtin gene, which leads to a polyglutamine expansion in the huntingtin protein. The exact mechanism by which mutant huntingtin causes HD is unknown, but it causes abnormalities in gene transcription as well as both mitochondrial dysfunction and oxidative damage. Because the penetrance of HD is complete with CAG repeats greater than 39, patients can be diagnosed well before disease onset with genetic testing. Longitudinal studies of HD patients before disease onset have shown that subtle cognitive and motor deficits occur as much as 10 years before onset, as do reductions in glucose utilization and striatal atrophy. An increase in inflammation, as shown by elevated interleukin-6, occurs approximately 15 years before onset. Detection of these abnormalities may be useful in defining an optimal time for disease intervention to try to slow or halt the degenerative process. Although reducing gene expression with small interfering RNA or short hairpin RNA is an attractive approach, other approaches targeting energy metabolism, inflammation, and oxidative damage may be more easily and rapidly moved into the clinic. The recent PREQUEL study of coenzyme Q10 in presymptomatic gene carriers showed the feasibility of carrying out clinical trials to slow or halt onset of HD. We review both the earliest detectable clinical and laboratory manifestations of HD, as well as potential neuroprotective therapies that could be utilized in presymptomatic HD.

Topics: Animals; Disease Models, Animal; Genetic Testing; Humans; Huntington Disease; Mitochondria; Neuroprotective Agents; Ubiquinone

Huntington's disease (HD) is a neurodegenerative genetic disorder caused by an expansion of CAG repeats in the HD gene encoding for huntingtin (Htt), resulting in progressive death of striatal neurons, with clinical symptoms of chorea, dementia and dramatic weight loss. Metabolic and mitochondrial dysfunction caused by the expanded polyglutamine sequence have been described along with other mechanisms of neurodegeneration previously described in human tissues and animal models of HD. In this review, we focus on mitochondrial and metabolic disturbances affecting both the central nervous system and peripheral cells, including mitochondrial DNA damage, mitochondrial complexes defects, loss of calcium homeostasis and transcriptional deregulation. Glucose abnormalities have also been described in peripheral tissues of HD patients and in HD animal and cellular models. Moreover, there are no effective neuroprotective treatments available in HD. Thus, we briefly discuss the role of creatine and coenzyme Q10 that target mitochondrial dysfunction and impaired bioenergetics and have been previously used in HD clinical trials.

Topics: Animals; Creatine; Disease Models, Animal; Humans; Huntington Disease; Metabolic Diseases; Mitochondrial Diseases; Nerve Tissue; Ubiquinone

Currently, assessment of new drug efficacy in glaucoma relies on conventional perimetry to monitor visual field changes. However, visual field defects cannot be detected until 20-40% of retinal ganglion cells (RGCs), the key cells implicated in the development of irreversible blindness in glaucoma, have been lost. We have recently developed a new, noninvasive real-time imaging technology, which is named DARC (detection of apoptosing retinal cells), to visualize single RGC undergoing apoptosis, the earliest sign of glaucoma. Utilizing fluorescently labeled annexin 5 and confocal laser scanning ophthalmoscopy, DARC enables evaluation of treatment effectiveness by monitoring RGC apoptosis in the same living eye over time. Using DARC, we have assessed different neuroprotective therapies in glaucoma-related animal models and demonstrated DARC to be a useful tool in screening neuroprotective strategies. DARC will potentially provide a meaningful clinical end point that is based on the direct assessment of the RGC death process, not only being useful in assessing treatment efficacy, but also leading to the early identification of patients with glaucoma. Clinical trials of DARC in glaucoma patients are due to start in 2008.

Topics: Amyloid beta-Peptides; Animals; Apoptosis; Clinical Trials as Topic; Disease Models, Animal; Glaucoma; Glutamic Acid; Humans; Lasers; Neuroprotective Agents; Ophthalmoscopes; Ophthalmoscopy; Retinal Ganglion Cells; Ubiquinone; Visual Field Tests; Visual Fields; Vitamins

Since the identification of the genetic mutation causing Friedreich's ataxia (FRDA) our understanding of the mechanisms underlying disease pathogenesis have improved markedly. The genetic abnormality results in the deficiency of frataxin, a protein targeted to the mitochondrion. There is extensive evidence that mitochondrial respiratory chain dysfunction, oxidative damage and iron accumulation play significant roles in the disease mechanism. There remains considerable debate as to the normal function of frataxin, but it is likely to be involved in mitochondrial iron handling, antioxidant regulation, and/or iron sulphur centre regulation. Therapeutic avenues for patients with FRDA are beginning to be explored in particular targeting antioxidant protection, enhancement of mitochondrial oxidative phosphorylation, iron chelation and more recently increasing FRDA transcription. The use of quinone therapy has been the most extensively studied to date with clear benefits demonstrated using evaluations of both disease biomarkers and clinical symptoms, and this is the topic that will be covered in this review.

Topics: Animals; Ataxia; Benzoquinones; Coenzymes; Disease Models, Animal; Friedreich Ataxia; Humans; Iron; Mutation; Neurodegenerative Diseases; Oxidative Stress; Oxygen; Quinones; Time Factors; Ubiquinone; Vitamin E

Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra zona compacta, and in other sub-cortical nuclei associated with a widespread occurrence of Lewy bodies. The cause of cell death in Parkinson's disease is still poorly understood, but a defect in mitochondrial oxidative phosphorylation and enhanced oxidative and nitrative stresses have been proposed. We have studied control(wt) (C57B1/6), metallothionein transgenic (MTtrans), metallothionein double gene knock (MTdko), alpha-synuclein knock out (alpha-syn(ko)), alpha-synuclein-metallothionein triple knock out (alpha-syn-MTtko), weaver mutant (wv/wv) mice, and Ames dwarf mice to examine the role of peroxynitrite in the etiopathogenesis of Parkinson's disease and aging. Although MTdko mice were genetically susceptible to 1, methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism, they did not exhibit any overt clinical symptoms of neurodegeneration and gross neuropathological changes as observed in wv/wv mice. Progressive neurodegenerative changes were associated with typical Parkinsonism in wv/wv mice. Neurodegenerative changes in wv/wv mice were observed primarily in the striatum, hippocampus and cerebellum. Various hallmarks of apoptosis including caspase-3, TNFalpha, NFkappaB, metallothioneins (MT-1, 2) and complex-1 nitration were increased; whereas glutathione, complex-1, ATP, and Ser(40)-phosphorylation of tyrosine hydroxylase, and striatal 18F-DOPA uptake were reduced in wv/wv mice as compared to other experimental genotypes. Striatal neurons of wv/wv mice exhibited age-dependent increase in dense cored intra-neuronal inclusions, cellular aggregation, proto-oncogenes (c-fos, c-jun, caspase-3, and GAPDH) induction, inter-nucleosomal DNA fragmentation, and neuro-apoptosis. MTtrans and alpha-Syn(ko) mice were genetically resistant to MPTP-Parkinsonism and Ames dwarf mice possessed significantly higher concentrations of striatal coenzyme Q10 and metallothioneins (MT 1, 2) and lived almost 2.5 times longer as compared to control(wt) mice. A potent peroxynitrite ion generator, 3-morpholinosydnonimine (SIN-1)-induced apoptosis was significantly attenuated in MTtrans fetal stem cells. These data are interpreted to suggest that peroxynitrite ions are involved in the etiopathogenesis of Parkinson's disease, and metallothionein-mediated coenzyme Q10 synthesis may provide neuroprotection.

Topics: alpha-Synuclein; Animals; Apoptosis; Brain; Coenzymes; Disease Models, Animal; Dopamine; Gene Expression Regulation; Humans; Metallothionein; Mice; Mice, Neurologic Mutants; Mice, Transgenic; MPTP Poisoning; Nerve Tissue Proteins; Parkinson Disease; Synucleins; Ubiquinone

The pathogenesis of Parkinson's disease (PD) remains obscure, but there is increasing evidence that impairment of mitochondrial function, oxidative damage, and inflammation are contributing factors. The present paper reviews the experimental and clinical evidence implicating these processes in PD. There is substantial evidence that there is a deficiency of complex I activity of the mitochondrial electron transport chain in PD. There is also evidence for increased numbers of activated microglia in both PD postmortem tissue as well as in animal models of PD. Impaired mitochondrial function and activated microglia may both contribute to oxidative damage in PD. A number of therapies targeting inflammation and mitochondrial dysfunction are efficacious in the MPTP model of PD. Of these, coenzyme Q(10) appears to be particularly promising based on the results of a recent phase 2 clinical trial in which it significantly slowed the progression of PD.

Topics: Animals; Anti-Inflammatory Agents; Coenzymes; Creatine; Disease Models, Animal; Free Radicals; Humans; Inflammation; Mitochondria; Oxidative Stress; Parkinson Disease; Ubiquinone

The concepts of energy dysregulation and oxidative stress and their complicated interdependence have rapidly evolved to assume primary importance in understanding the pathophysiology of numerous neurological disorders. Therefore, neuroprotective strategies addressing specific bioenergetic defects hold particular promise in the treatment of these conditions (i.e., amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, Friedreich's ataxia, mitochondrial cytopathies and other neuromuscular diseases), all of which, to some extent, share 'the final common pathway' leading to cell death through either necrosis or apoptosis. Compounds such as creatine monohydrate and coenzyme Q(10) offer substantial neuroprotection against ischaemia, trauma, oxidative damage and neurotoxins. Miscellaneous agents, including alpha-lipoic acid, beta-OH-beta-methylbutyrate, riboflavin and nicotinamide, have also been shown to improve various metabolic parameters in brain and/or muscle. This review will highlight the biological function of each of the above mentioned compounds followed by a discussion of their utility in animal models and human neurological disease. The balance of this work will be comprised of discussions on the therapeutic applications of creatine and coenzyme Q(10).

Topics: Amyotrophic Lateral Sclerosis; Animals; Coenzymes; Creatine; Disease Models, Animal; Energy Metabolism; Humans; Huntington Disease; Nervous System Diseases; Neuroprotective Agents; Ubiquinone

Topics: Animals; Coenzymes; Cricetinae; Disease Models, Animal; Female; Follow-Up Studies; Heart Failure; Heart Function Tests; Hemodynamics; Humans; Male; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis; Treatment Outcome; Ubiquinone

Huntington's disease (HD) is a prototypical neurodegenerative disease characterized by selective loss of neurons in the basal ganglia. Although the gene defect has recently been identified, the mechanism by which it leads to neuronal degeneration remains unknown. We have hypothesized that a defect in oxidative phosphorylation may lead to slow, excitotoxic neuronal degeneration in this illness. Evidence for such a defect is reviewed here, including our recent studies using magnetic resonance imaging spectroscopy that show elevated lactate levels in the basal ganglia and cerebral cortex of patients with HD. If a defect in energy metabolism is responsible for neuronal degeneration in HD, it should be possible to mimic the neurodegenerative process with mitochondrial toxins. Our recent studies with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase, show that it can produce striking similarities to the neuropathologic and neurochemical features of HD in both rodents and primates. If such a mechanism is indeed relevant to the pathogenesis of HD, then agents that can improve oxidative phosphorylation might prove to be efficacious. We found that both coenzyme Q10 and nicotinamide can ameliorate striatal lesions produced by mitochondrial toxins in vivo. Furthermore, they reduced elevated lactate concentrations when administered to patients with HD. This finding raises the possibility that such an approach might prove useful in trying to slow the neurodegenerative process.

Topics: Animals; Coenzymes; Disease Models, Animal; Energy Metabolism; Humans; Huntington Disease; Mitochondria; Neurotoxins; Niacinamide; Nitro Compounds; Propionates; Ubiquinone

Niemann-Pick disease, type C1 (NPC1), which arises from a mutation in the NPC1 gene, is characterized by abnormal cellular storage and transport of cholesterol and other lipids that leads to hepatic disease and progressive neurological impairment. Oxidative stress has been hypothesized to contribute to the NPC1 disease pathological cascade. To determine whether treatments reducing oxidative stress could alleviate NPC1 disease phenotypes, the in vivo effects of the antioxidant N-acetylcysteine (NAC) on two mouse models for NPC1 disease were studied. NAC was able to partially suppress phenotypes in both antisense-induced (NPC1ASO) and germline (Npc1-/-) knockout genetic mouse models, confirming the presence of an oxidative stress-related mechanism in progression of NPC1 phenotypes and suggesting NAC as a potential molecule for treatment. Gene expression analyses of NAC-treated NPC1ASO mice suggested NAC affects pathways distinct from those initially altered by Npc1 knockdown, data consistent with NAC achieving partial disease phenotype suppression. In a therapeutic trial of short-term NAC administration to NPC1 patients, no significant effects on oxidative stress in these patients were identified other than moderate improvement of the fraction of reduced CoQ10, suggesting limited efficacy of NAC monotherapy. However, the mouse model data suggest that the distinct antioxidant effects of NAC could provide potential treatment of NPC1 disease, possibly in concert with other therapeutic molecules at earlier stages of disease progression. These data also validated the NPC1ASO mouse as an efficient model for candidate NPC1 drug screening, and demonstrated similarities in hepatic phenotypes and genome-wide transcript expression patterns between the NPC1ASO and Npc1-/- models.

Topics: Acetylcysteine; Adolescent; Adult; Animals; Child; Child, Preschool; Cross-Over Studies; Disease Models, Animal; Double-Blind Method; Female; Gene Expression; Humans; Liver; Male; Mice; Mice, Knockout; Niemann-Pick Disease, Type C; Oxidative Stress; Ubiquinone; Young Adult

Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism.

Topics: Animals; Coenzymes; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Hemodynamics; Myocardial Ischemia; Myocardial Stunning; Random Allocation; Swine; Ubiquinone

Aging is the major risk factor for Alzheimer's disease (AD), and cognitive and memory impairments are common among the elderly. Interestingly, coenzyme Q10 (Q10) levels decline in the brain of aging animals. Q10 is a substantial antioxidant substance, which has an important role in the mitochondria.. We assessed the possible effects of Q10 on learning and memory and synaptic plasticity in aged β-amyloid (Aβ)-induced AD rats.. In this study, 40 Wistar rats (24-36 months old; 360-450 g) were randomly assigned to four groups (n = 10 rats/group)-group I: control, group II: Aβ, group III: Q10; 50 mg/kg, and group IV: Q10+Aβ. Q10 was administered orally by gavage daily for 4 weeks before the Aβ injection. The cognitive function and learning and memory of the rats were measured by the novel object recognition (NOR), Morris water maze (MWM), and passive avoidance learning (PAL) tests. Finally, malondialdehyde (MDA), total antioxidant capacity (TAC), total thiol group (TTG), and total oxidant status (TOS) were measured.. Q10 improved the Aβ-related decrease in the discrimination index in the NOR test, spatial learning and memory in the MWM test, passive avoidance learning and memory in the PAL test, and long-term potentiation (LTP) impairment in the hippocampal PP-DG pathway in aged rats. In addition, Aβ injection significantly increased serum MDA and TOS levels. Q10, however, significantly reversed these parameters and also increased TAC and TTG levels in the Aβ+Q10 group.. Our experimental findings suggest that Q10 supplementation can suppress the progression of neurodegeneration that otherwise impairs learning and memory and reduces synaptic plasticity in our experimental animals. Therefore, similar supplemental Q10 treatment given to humans with AD could possibly provide them a better quality of life.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Child, Preschool; Disease Models, Animal; Hippocampus; Humans; Long-Term Potentiation; Maze Learning; Memory Disorders; Neuronal Plasticity; Quality of Life; Rats; Rats, Wistar

We aimed to create a mechanical optic nerve damage model in rats and to investigate the neuroprotective effects of topical Coenzyme Q10 + Vitamin E TPGS (CoQ10+Vit E) molecule on retinal ganglion cells. In our study, 30 eyes of 20 male Wistar rats were used. Three groups, each consisting of 10 eyes, were formed as control, experimental, and treatment groups. The control group was used to test the formation of optic nerve damage. Topical CoQ10 + Vit E TPGS solution was applied to the rats in the treatment group, one drop twice a day for 3 weeks. On the other hand, physiological drops were applied to the experimental group 2 times a day for 3 weeks. After 3 weeks, the optic nerves of the rats were dissected and examined histopathologically. In electron microscopic examination of the treatment group, it was noted that the myelin sheath in the majority of myelinated nerve fibers and the normal structures of mitochondria, neurotubules, and neurofilaments in the axoplasm were preserved. It was observed that the oligodendrocytes surrounded the myelinated axons. In the experimental group, significant degenerative changes were observed in myelinated nerve fibers in many areas. The number of myelinated axons was significantly increased in the treatment group compared to the experimental group (p = .0028). In the light of the data obtained, the neuroprotective effect of the topically used CoQ10 + Vit E TPGS molecule was found to be histopathologically effective in our experimental study.

Topics: Animals; Disease Models, Animal; Male; Optic Neuropathy, Ischemic; Rats; Rats, Wistar; Ubiquinone; Vitamin E

Recent studies have demonstrated that airway basal stem cells (BCs) transplantation can ameliorate bleomycin-induced idiopathic pulmonary fibrosis (IPF) through lung regeneration promotion. However, BCs under oxidative stress in the alveolar microenvironment are poor in survival, causing unsatisfied efficacy of BCs transplantation. In this study, we investigated whether Coenzyme Q10(CoQ10) counteracts oxidative stress in the alveolar microenvironment, thus improved the efficacy of BCs transplantation for IPF treatment.. The protective effects of CoQ10 on H. CoQ10 blocked H

Topics: Animals; Apoptosis; Bleomycin; Cells, Cultured; Disease Models, Animal; Humans; Idiopathic Pulmonary Fibrosis; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Regeneration; Stem Cell Transplantation; Ubiquinone

Alzheimer's disease (AD) is a degenerative disease that causes memory and learning impairments as well as dementia. Coenzyme Q10 (CoQ10) is an anti-inflammatory and anti-oxidative stress supplement that can improve inflammation and oxidative stress associated with AD. This study investigated the effects of drug delivery of COQ10 by exosomes derived from adipose-derived stem cells (ADSCs-Exo) on cognition, memory, and neuronal proliferation in a rat model of Streptozotocin (STZ)-induced AD. Since the establishment of the AD model, the rats have received intraperitoneal injections of CoQ10, Exo, or CoQ10-loaded ADSCs-Exo (Exo+ CoQ10). The passive avoidance test and the Morris water maze (MWM) were used to assess memory and cognition changes. Cell density was determined using histological methods. The expression of BDNF was measured using an ELISA kit. SOX2 expression was determined using immunohistochemistry. According to the results of the MWM and passive avoidance task, Exo+CoQ10 significantly improved STZ-induced memory impairment compared to CoQ10 and Exo groups alone. Furthermore, BDNF expression increased in the STZ-induced rats after Exo+ CoQ10, when compared to the CoQ10 and Exo groups. In addition, Exo+CoQ10 had the highest cell density and SOX2 gene expression, when compared to the CoQ10 and Exo groups. According to the findings of this study, Exo+ COQ10 enhanced cognition and memory deficiency in Alzheimer's disease by boosting BDNF and SOX2 levels in the hippocampus. Hence, the use of exosomes derived from adipose-derived stem cells as the carrier of CoQ10 may increase the therapeutic effect of CoQ10, which can possibly be due to the regenerative properties of the exosomes.

Topics: Alzheimer Disease; Animals; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Exosomes; Neuroprotective Agents; Rats; Stem Cells; Streptozocin; Ubiquinone

Osteoarthritis (OA) is the most common degenerative joint disease and is characterized by breakdown of joint cartilage. Coenzyme Q10 (CoQ10) exerts diverse biological effects on bone and cartilage; observational studies have suggested that CoQ10 may slow OA progression and inflammation. However, any effect of CoQ10 on OA remains unclear. Here, we investigated the therapeutic utility of CoQ10-micelles.. Seven-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. CoQ10-micelles were administered orally to MIA-induced OA rats; celecoxib served as the positive control. Pain, tissue destruction, and inflammation were measured. The expression levels of catabolic and inflammatory cell death markers were assayed in CoQ10-micelle-treated chondrocytes.. Oral supplementation with CoQ10-micelles attenuated OA symptoms remarkably, including pain, tissue destruction, and inflammation. The expression levels of the inflammatory cytokines IL-1β, IL-6, and MMP-13, and of the inflammatory cell death markers RIP1, RIP3, and pMLKL in synovial tissues were significantly reduced by CoQ10-micelle supplementation, suggesting that CoQ10-micelles might attenuate the synovitis of OA. CoQ10-micelle addition to cultured OA chondrocytes reduced the expression levels of catabolic and inflammatory cell death markers.. CoQ10-micelles might usefully treat OA.

Topics: Animals; Cartilage, Articular; Cell Death; Chondrocytes; Disease Models, Animal; Inflammation; Iodoacetic Acid; Male; Micelles; Nociceptive Pain; Osteoarthritis; Rats; Rats, Wistar; Ubiquinone

The aim of this study was to investigate the effect of coenzyme Q10 (CoQ10), a commonly used nutritional supplement, on intracranial aneurysm (IA) initiation and progression in a mouse model, as well as the mechanism.. CoQ10 promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes. In H. CoQ10 is effective in reducing oxidative stress in VSMCs, thereby attenuating IA formation and rupture in mice. CoQ10 also alleviates inflammation and restores normal phenotypes of VSMCs in the cerebral arteries. Our data suggest that CoQ10 is a potentially effective drug for managing IA.. To investigate the effect of CoQ10, a commonly used nutritional supplement, on IA initiation and progression in a mouse model, as well as the mechanism. CoQ10 promoted the expression of Nrf2 and antioxidant enzymes. In H

Topics: Animals; Antioxidants; Disease Models, Animal; Hydrogen Peroxide; Intracranial Aneurysm; Mice; Oxidative Stress; Ubiquinone

To evaluate the efficacy of antioxidants in cellular-level post-ischemia/reperfusion injury of the testis and to validate these effects with. Fifty-six adult male rats were randomly divided into seven groups-Group 1: sham; Group 2: ischemia/reperfusion only group; Group 3: ischemia was induced and vitamin E (100 mg/kg) was administered intraperitoneally 30 min before reperfusion; Group 4: vitamin E was given intraperitoneally without ischemia/reperfusion; Group 5: ischemia was induced and coenzyme Q10 (10 mg/body weight) was administered intraperitoneally 30 min before reperfusion; Group 6: coenzyme Q10 was administered intraperitoneally without ischemia/reperfusion; Group 7: ischemia was induced and coenzyme Q10 + vitamin E was administered intraperitoneally 30 min before reperfusion. After detorsion, fluorodeoxyglucose was applied to all groups according to the animals' weight and fluorodeoxyglucose positron emission tomography was performed after 1 h. In pursuit of imaging, orchiectomy was performed for histopathological and biochemical evaluations.. A significant effect of group on catalase, maximum standardized uptake value, and seminiferous tubule diameters (p < 0.005) was observed. According to this, combining ischemia/reperfusion with vitamin E increased the maximum standardized uptake value significantly higher than in all other groups; in addition, catalase was significantly higher than in Groups 4-6. Histopathological outcomes revealed that "sham" had significantly larger seminiferous tubule diameter than Groups 2-4. Also, "ischemia/reperfusion" was the only group which had significantly smaller seminiferous tubule diameters than Groups 6 and 7.. In contrast to vitamin E, coenzyme Q10 provided remarkable regression of oxidative stress-induced enzymes and revealed consistent effects on histopathological outcomes, which were validated with fluorodeoxyglucose positron emission tomography imaging.

Topics: Animals; Disease Models, Animal; Fluorodeoxyglucose F18; Glucose; Male; Positron-Emission Tomography; Radiopharmaceuticals; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Testis; Ubiquinone; Vitamin E; Vitamins

Multiple Sclerosis (MS) is a chronic, progressive demyelinating disease of the central nervous system that causes the most disability in young people, besides trauma. Coenzyme Q10 (CoQ10)-also known as ubiquinone-is an endogenous lipid-soluble antioxidant in the mitochondrial oxidative respiratory chain which can reduce oxidative stress and inflammation, the processes associated with demyelination in MS. Cuprizone (CPZ) intoxication is a well-established model of inducing MS, best for studying demyelination-remyelination. In this study, we examined for the first time the role of CoQ10 in preventing demyelination and induction of remyelination in the chronic CPZ model of MS. 40 male mice were divided into four groups. 3 group chewed CPZ-containing food for 12 weeks to induce MS. After 4 weeks, one group were treated with CoQ10 (150 mg/kg/day) by daily gavage until the end of the experiment, while CPZ poisoning continued. At the end of 12 weeks, tail suspension test (TST) and open field test (OFT) was taken and animals were sacrificed to assess myelin basic protein (MBP), oligodendrocyte transcription factor-1 (Olig1), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) by real-time polymerase chain reaction (real-time PCR) and total antioxidant capacity (TAC) and superoxide dismutase (SOD) by Elisa test. Luxol fast blue (LFB) staining was used to evaluate histological changes. CoQ10 administration promoted remyelination in histological findings. MBP and Olig-1 expression were increased significantly in CoQ10 treated group compare to the CPZ-intoxicated group. CoQ10 treatment alleviated stress oxidative status induced by CPZ and dramatically suppress inflammatory biomarkers. CPZ ingestion made no significant difference between normal control group and the CPZ-intoxicated group in TST and OFT. CoQ10 can enhance remyelination in the CPZ model and potentially might have same effects in MS patients.

Topics: Animals; Behavior, Animal; Biomarkers; Chronic Disease; Corpus Callosum; Cuprizone; Cytokines; Demyelinating Diseases; Disease Models, Animal; Inflammation; Inflammation Mediators; Mice, Inbred C57BL; Multiple Sclerosis; Myelin Sheath; Oxidative Stress; Remyelination; Ubiquinone

Radiation enteropathy is one the most common clinical issue for patients receiving radiotherapy for abdominal/pelvic tumors which severely affect the quality of life of cancer patients due to dysplastic lesions (ischemia, ulcer, or fibrosis) that aggravate the radiation damage. Herein, this study demonstrated the prophylactic role of coenzyme Q10 (CoQ10), a powerful antioxidant, against radiotherapy-induced gastrointestinal injury. Male Sprague Dawley rats were divided into four groups: group 1 was defined as control, and group 2 was the irradiated group. Group 3 and 4 were CoQ10 control and radiation plus CoQ10 groups, respectively. CoQ10 (10 mg/kg) was orally administered for 10 days before 10 Gy whole-body radiation and was continued for 4 days post-irradiation. CoQ10 administration protected rats delivered a lethal dose of ϒ-radiation from changes in crypt-villus structures and promoted regeneration of the intestinal epithelium. CoQ10 attenuated radiation-induced oxidative stress by decreasing lipid peroxidation and increasing the antioxidant enzyme catalase activity and reduced glutathione level. CoQ10 also counteracts inflammatory response mediated after radiation exposure through downregulating intestinal NF-ĸB expression which subsequently decreased the level of inflammatory cytokine IL-6 and the expression of COX-2. Radiation-induced intestinal fibrosis confirmed via Masson's trichrome staining occurred through upregulating transforming growth factor (TGF)-β1 and matrix metalloproteinase (MMP)-9 expression, while CoQ10 administration significantly diminishes these effects which further confirmed the anti-fibrotic property of CoQ10. Therefore, CoQ10 is a promising radioprotector that could prevent intestinal complications and enhance the therapeutic ratio of radiotherapy in patients with pelvic tumors through suppressing the NF-kB/TGF-β1/MMP-9 signaling pathway.

Topics: Animals; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Inflammation; Intestinal Diseases; Male; Matrix Metalloproteinase 9; NF-kappa B; Radiation Injuries; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta; Ubiquinone; Vitamins

The increase in some factors following cerebral ischemia, especially Matrix metalloproteinase (MMPs) and inflammatory factors lead to blood-brain barrier (BBB) damages, edema and neuronal death. Previous studies have shown that these molecules are miRNA-149-5p (miR-149) and Coenzyme (Co) Q10 targets. Therefore, in this study, the effect of mimic of miRNA-149-5p (mimic miR) and CoQ10 on the expression of metalloproteinase 1 and 2 and inflammatory cytokines following injury caused by cerebral ischemia is investigated. Cerebral ischemia was modeled by Middle Cerebral Artery Occlusion (MCAO). Male Wistar rats were randomly divided into 6 groups: sham (without surgery and treatment), control (MCAO), negative control (NC): MCAO + scrambled miR, vehicle: MCAO + Ethanole, first treatment: MCAO + mimic miR, second treatment: MCAO + Q10. Each group was divided into 6 subgroups to evaluate neurological defects, the volume of tissue damage using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, blood-brain barrier permeability using cerebral Evans Blue (EB) staining, edema by measuring the percentage of brain water, MMP-2,9 mRNA and miR-149-5p levels using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the levels of IL-6 and TNF-α proteins using ELISA. The data obtained from this study showed that the use of mimic miR and Q10 increased the level of miR-149, decreased the extent of neurological defects and tissue damage, increased BBB integrity, decreased brain water percentage and also decreased the level of inflammatory cytokines and MMPs. It seems that the use mimic of miRNA-149-5p and Q10 can have a protective effect on the brain by reducing MMPs and inflammatory factors following cerebral ischemia and this could lead to a new treatment strategy to reduce the complications of cerebral ischemia.

Topics: Animals; Blood-Brain Barrier; Brain; Brain Edema; Brain Ischemia; Cytokines; Disease Models, Animal; Male; Metalloproteases; MicroRNAs; Neuroprotective Agents; Rats; Rats, Wistar; Ubiquinone

Several studies have shown that coenzyme Q10 (CoQ10) can rescue ovarian aging and that ovarian surface epithelium (OSE)-derived ovarian stem cells (OSCs) are useful for treating infertility due to ovarian aging. However, few studies have examined the effect of CoQ10 on OSCs. This study was aimed to investigate whether CoQ10 activates OSCs and recovers ovarian function in a 4-vinylcyclohexene diepoxide (VCD)-induced mouse model of ovarian failure.. Forty female C57BL/6 mice aged 6 weeks were randomly divided into four groups (n = 10/group): a control group administered saline orally, a CoQ10 group administered 150 mg/kg/day of CoQ10 orally in 1 mL of saline daily for 14 days, a VCD group administered 160 mg/kg/day of VCD i.p. in 2.5 mL of saline/kg for 5 days, and a VCD + CoQ10 group administered VCD i.p. for 5 days injection and CoQ10 (150 mg/kg/day) orally for 14 days. After treatment, follicle counts were evaluated by hematoxylin and eosin (H&E) staining, and ovarian mRNA expressions of Bmp-15, Gdf-9, and c-Kit were examined by quantitative real-time PCR. Serum FSH, AMH, and ROS levels were also measured. Oocyte-like structure counts and the expressions of Oct-4 and MVH were also evaluated after culturing OSE for 3 weeks. In a second experiment, 32 female mice were administered CoQ10 as described above, induced to superovulate using PMSG and hCG, and mated. Numbers of zygotes and embryo development rate were examined.. Postcultured OSE showed significant increases in the numbers of oocyte-like structure and that the expression of Oct-4 and MVH were higher in the VCD + CoQ10 group than in the VCD group (p < 0.05). Numbers of surviving follicles from primordial to antral follicles, numbers of zygotes retrieved and embryo development rate to blastocyst were significantly greater in the VCD + CoQ10 group than in the VCD group (p < 0.01). Serum AMH level and ovarian expressions of Bmp-15, Gdf-9 and c-Kit were also significantly greater in the VCD + CoQ10 group than in the VCD group (p < 0.05). In contrast, serum ROS level was significantly lower in the VCD + CoQ10 group than in the VCD group (p < 0.05).. This study shows that CoQ10 stimulates the differentiation of OSE-derived OSCs and confirms that CoQ10 can reduce ROS levels and improve ovarian function and oocyte quality in mice with VCD-induced ovarian failure.

Topics: Animals; Cells, Cultured; Cyclohexenes; Disease Models, Animal; Epithelium; Female; In Vitro Oocyte Maturation Techniques; Mice; Mice, Inbred C57BL; Oocytes; Ovarian Diseases; Ovary; Stem Cells; Ubiquinone; Vinyl Compounds

In this study, it was aimed to investigate the effect of coenzyme Q10 (CoQ10) on cisplatin-induced oxidative retinal damage in rats biochemically and histopathologically.. Thirty male Wistar albino rats were divided into 3 groups randomly: untreated control (C group), only 2.5 mg/kg cisplatin daily administrated group for 2 weeks (CP group), 2.5 mg/kg cisplatin + 20 mg/kg orally CoQ10 daily administrated group for 2 weeks (CoQC group). At the end of experimental period, blood samples obtained before sacrification for the biochemical examination of serum malondialdehyde (MDA), total glutathione (tGSH), total oxidant system (TOS), total antioxidant systemic (TAS) levels and after eyes were removed for examined histopathology.. As a result of our study, severe histopathological damage was detected in the retinal tissue of the cisplatin group with serum malondialdehyde (MDA) and total oxidant system (TOS) levels were high and total glutathione (tGSH) and total antioxidant systemic (TAS) levels were low. However, it was observed that the histopathological damage associated with cisplatin was decreased in the retinal tissue of the CoQ10 group, which inhibited the increase in blood serum MDA/TOS levels and decrease in tGSH/TAS levels.. The biochemical and histopathological results of our study were compatible with each other, so we concluded that the damage to the rat retinal tissue caused by cisplatin may be reversible with coenzyme.

Topics: Administration, Oral; Animals; Antioxidants; Cisplatin; Disease Models, Animal; Humans; Male; Oxidative Stress; Rats; Retina; Retinal Diseases; Ubiquinone

Doxorubicin (DOX) is used as an anticancer drug despite its several side effects, especially its irreversible impacts on cardiotoxicity. Coenzyme Q10 (Q10) as a powerful antioxidant and lisinopril (LIS) as an angiotensin-converting enzyme inhibitor seem to provide protection against DOX-induced cardiotoxicity. Therefore, this study aimed to assess the cardioprotective effects of Q10 and LIS against DOX-induced cardiotoxicity in rats. Adult male Sprague-Dawley rats were randomly assigned into the control, LIS, Q10, DOX, DOX + LIS, and DOX + Q10 groups. On day 21, ECG was recorded and the right ventricle was dissected for evaluation of catalase activity and malondialdehyde (MDA) concentration. Additionally, the left ventricle and the sinoatrial (SA) node were dissected to assess the stereological parameters. The results of ECG indicated bradycardia and increase in QRS duration and QT interval in the DOX group compared to the control group. Meanwhile, the total volumes of the left ventricle, myocytes, and microvessels and the number of cardiomyocyte nuclei decreased, whereas the total volume of the connective tissue and the mean volume of cardiomyocytes increased in the DOX group. On the other hand, the SA node and the connective tissue were enlarged, while the volume of the SA node nuclei was reduced in the DOX group. Besides, catalase activity was lower and MDA concentration was higher in the DOX-treated group. Q10 could recover most stereological parameters, catalase activity, and MDA concentration. LIS also prevented some stereological parameters and ECG changes and improved catalase activity and MDA concentration in the DOX group. The findings suggested that Q10 and LIS exerted cardioprotective effects against DOX-induced cardiac toxicity.

Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Catalase; Disease Models, Animal; Doxorubicin; Electrocardiography; Heart Conduction System; Heart Diseases; Heart Rate; Lisinopril; Male; Malondialdehyde; Myocytes, Cardiac; Rats, Sprague-Dawley; Ubiquinone

Parkinson's disease (PD) is a complex neurodegenerative disease in which the understanding of the underlying molecular mechanisms can be constructive in the diagnosis and treatment. Matrix metalloproteinase (MMPs) elevation and damage to the blood-brain barrier (BBB) are critical mechanisms involved in the PD separation. Studies have revealed that changes in miR-149-5p and CoQ10 are associated with BBB damage, and CoQ10 can affect the levels of some miRs. Hence, in the present study, we aimed to evaluate CoQ10 and miR-149-5p mimic on miR-149-5p, MMPs and TH expression, and behavioral functions of the PD models. PD was induced by injection of 6-OHDA into the rats' Medial Forbrain Bundle (MFB). The behavioral tests, including the Rotation test, Rotarod test, and Open field test, have been directed two weeks after PD induction. Next, the MiR-149-5p mimic (miR-mimic) and CoQ10 have been administered to rats. The same behavioral tests have been evaluated two weeks after administration to investigate the effect of miR-149-5p mimic and CoQ10. The rats were followed extra four weeks, and the behavioral tests have performed again. Finally, the expression of MMPs and miR-149-5p genes was measured using RT-qPCR, and tyrosine hydroxylase (TH) was assessed through immunohistochemistry analysis. According to the obtained results, the level of miR-149-5p has decreased, followed by PD induction in rats. RT-qPCR analysis has represented upregulation and downregulation of miR-149-5p and MMP-2,9, respectively, after miR-mimic and CoQ10 treatment. The treated rats have also represented improved motor function and increased TH +  cells in the striatum according to the behavioral tests and immunohistochemistry assay. Taking together miR-149 and CoQ10 has shown to have an impressive potential to prevent damage to dopaminergic neurons caused by 6-OHDA injection through reducing MMP-2,9, increased TH expression, and improved motor function.

Topics: Animals; Disease Models, Animal; Matrix Metalloproteinases; MicroRNAs; Neurodegenerative Diseases; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Rats; Ubiquinone

In the present study, we investigated the cardioprotective effects of coenzyme Q10 (Q10) against doxorubicin (DOXO) induced cardiomyopathy. Twenty adult rats were distributed in four experimental groups: group 1 received NaCl 0.9% at 1 ml/day for 14 days; group 2 received Q10 at 1 mg/kg/day for 14 days; group 3 received initial 7 days of treatment with NaCl 0.9% followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of NaCl; and group 4 received initial 7 days of Q10 1 mg/kg/day, followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of Q10. At the end of 14 days, systolic, diastolic and mean blood pressure, electrocardiogram (ECG), complete blood count, and serum biochemical profile were evaluated. We also analyzed heart histological and ultrastructure analysis, and estimated heart's oxidative stress and lipid peroxidation. DOXO administration altered ECG, with increase heart rate, P-wave duration, PR interval duration, and T-wave amplitude. All the parameters were significantly reduced following Q10 treatment. DOXO also caused increase in CK, CK-MB, LDH, and urea levels, which were not mitigated by Q10 treatment. However, Q10 reduced oxidative stress by interfering with superoxide dismutase, significantly decreasing lipid peroxidation in heart tissue. DOXO administration also leads to several histological and ultrastructure alterations including cardiomyocyte degeneration and intense intracelullar autophagosomes, all minimized by Q10 treatment. Q10 treatment prevented the ECG changes, minimized oxidative stress, lipid peroxidation, and DOXO-induced heart tissue alterations. Our findings suggest that pre- and post-treatment with Q10 exerts potential cardioprotective effect against the DOX-induced cardiotoxicity.

Topics: Animals; Antioxidants; Cardiomyopathies; Cardiotoxicity; Disease Models, Animal; Doxorubicin; Lipid Peroxidation; Myocytes, Cardiac; Oxidative Stress; Rats, Wistar; Ubiquinone

A role for mitochondrial dysfunction has been proposed in the immune dysregulation and organ damage characteristic of systemic lupus erythematosus (SLE). Idebenone is a coenzyme Q10 synthetic quinone analog and an antioxidant that has been used in humans to treat diverse diseases in which mitochondrial function is impaired. This study was undertaken to assess whether idebenone ameliorates lupus in murine models.. Idebenone was administered orally to MRL/lpr mice at 2 different doses (1 gm/kg or 1.5 gm/kg idebenone-containing diet) for 8 weeks. At peak disease activity, clinical, immunologic, and metabolic parameters were analyzed and compared to those in untreated mice (n = 10 per treatment group). Results were confirmed in the lupus-prone NZM2328 mouse model.. In MRL/lpr mice, idebenone-treated mice showed a significant reduction in mortality incidence (P < 0.01 versus untreated mice), and the treatment attenuated several disease features, including glomerular inflammation and fibrosis (each P < 0.05 versus untreated mice), and improved renal function in association with decreased renal expression of interleukin-17A (IL-17A) and mature IL-18. Levels of splenic proinflammatory cytokines and inflammasome-related genes were significantly decreased (at least P < 0.05 and some with higher significance) in mice treated with idebenone, while no obvious drug toxicity was observed. Idebenone inhibited neutrophil extracellular trap formation in neutrophils from lupus-prone mice (P < 0.05) and human patients with SLE. Idebenone also improved mitochondrial metabolism (30% increase in basal respiration and ATP production), reduced the extent of heart lipid peroxidation (by one-half that of untreated mice), and significantly improved endothelium-dependent vasorelaxation (P < 0.001). NZM2328 mice exposed to idebenone also displayed improvements in renal and systemic inflammation, reducing the kidney pathology score (P < 0.05), IgG/C3 deposition (P < 0.05), and the gene expression of interferon, proinflammatory, and inflammasome-related genes (at least P < 0.05 and some with higher significance).. Idebenone ameliorates murine lupus disease activity and the severity of organ damage, supporting the hypothesis that agents that modulate mitochondrial biologic processes may have a therapeutic role in human SLE.

Topics: Animals; Antioxidants; Disease Models, Animal; Extracellular Traps; Inflammation; Interleukin-17; Interleukin-18; Kidney; Lupus Erythematosus, Systemic; Mice; Mice, Inbred MRL lpr; Mitochondria; Ubiquinone

Cornelian cherries (CCs) belong to promising anti-obesity substances. We aimed to study effects of coenzyme Q10 (CoQ10) and two varieties of CCs on lipid profile, ROS, and nitric oxide (NO) production in obese rats. Male Zucker rats were divided into the control group and groups treated with CoQ10 (30mg/kg/day), or CC varieties: Koralovij Marka (KM) and Wild Type (WT) (5 g/kg/day,

Topics: Animals; Blood Pressure; Cornus; Disease Models, Animal; Lipid Metabolism; Lipids; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase Type III; Obesity; Organ Size; Oxidative Stress; Plant Extracts; Rats; Rats, Zucker; Reactive Oxygen Species; Ubiquinone

Neonatal ischemic stroke has a higher incidence than childhood stroke. Seizures are the first sign for the need for clinical assessment in neonates, but many questions remain regarding treatments and follow-up modalities. In the absence of a known pathophysiological mechanism, only supportive care is currently provided. Stroke-induced microglia activation and neuroinflammation are believed to play a central role in the pathological progression of neonatal ischemic stroke. We induced a photothrombotic infarction with Rose Bengal in neonatal rats to investigate the effects of pre- and post-treatment with Aspirin (ASA), Clopidogrel (Clop), and Coenzyme Q10 (CoQ10), which are known for their neuroprotective effects in adult stroke. Pre-stroke medication ameliorates cerebral ischemic injury and reduces infarct volume by reducing microglia activation, cellular reactive oxygen species (ROS) production, and cytokine release. Post-stroke administration of ASA, Clop, and CoQ10 increased motor function and reduced the volume of infarction, and the statistical evidence was stronger than that seen in the pre-stroke treatment. In this study, we demonstrated that ASA, Clop, and CoQ10 treatment before and after the stroke reduced the scope of stroke lesions and increased behavioral activity. It suggests that ASA, Clop, and CoQ10 medication could significantly have neuroprotective effects in the neonates who have suffered strokes.

Topics: Animals; Animals, Newborn; Aspirin; Brain Ischemia; Clopidogrel; Disease Models, Animal; Inflammation; Neuroprotective Agents; Rats; Rose Bengal; Stroke; Ubiquinone

Fibromyalgia (FM) is one of the most common musculoskeletal pain conditions. Although the aetiology of FM is still unknown, mitochondrial dysfunction and the overproduction of reactive oxygen intermediates (ROI) are common characteristics in its pathogenesis. The reserpine experimental model can induce FM-related symptoms in rodents by depleting biogenic amines. However, it is unclear whether reserpine causes other pathophysiologic characteristics of FM. So far, no one has investigated the relevance of mitochondrial dysfunction in the reserpine-induced experimental FM model using protection- and insult-based mitochondrial modulators. Reserpine (1 mg/kg) was subcutaneously injected once daily for three consecutive days in male Swiss mice. We carried out analyses of reserpine-induced FM-related symptoms, and their modulation by using mitochondrial insult on ATP synthesis (oligomycin; 1 mg/kg, intraperitoneally) or mitochondrial protection (coenzyme Q10; 150 mg/kg/5 days, orally). We also evaluated the effect of reserpine on mitochondrial function using high-resolution respirometry and oxidative status. Reserpine caused nociception, loss in muscle strength, and anxiety- and depressive-like behaviours in mice that were consistent with clinical symptoms of FM, without inducing body weight and temperature alterations or motor impairment. Reserpine-induced FM-related symptoms were increased by oligomycin and reduced by coenzyme Q10 treatment. Reserpine caused mitochondrial dysfunction by negatively modulating the electron transport system and mitochondrial respiration (ATP synthesis) mainly in oxidative muscles and the spinal cord. These results support the role of mitochondria in mediating oxidative stress and FM symptoms in this model. In this way, reserpine-inducing mitochondrial dysfunction and increased production of ROI contribute to the development and maintenance of nociceptive, fatigue, and depressive-like behaviours.

Topics: Animals; Behavior, Animal; Depression; Disease Models, Animal; Fatigue; Fibromyalgia; Male; Mice; Mitochondria; Models, Biological; Muscles; Nociception; Oxidation-Reduction; Reserpine; Spinal Cord; Ubiquinone

Preeclampsia has ranked as one of the leading causes of both maternal and prenatal morbidity and mortality around the world. The hypotensive effect of coenzyme Q10 has been widely reported in preeclampsia rat model. However, the detailed mechanism remains unclear.. L-NAME was utilized to establish the preeclampsia rat model. Biomarker assessments were performed to identify the levels of vascular factors including soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PlGF), the circulating cytokines including interleukin 6, tumor necrosis factor α and interleukin 1β, and oxidative stress factors including malondialdehyde, H. Coenzyme Q10 treatment decreased the blood pressure in rat model with preeclampsia by regulating the circulating levels of sFlt-1 and PlGF. Coenzyme Q10 attenuated serum and placental inflammation and oxidative stress in L-NAME-induced preeclampsia rats. Coenzyme Q10 activated the placental Nrf2/HO-1 pathway in L-NAME-induced preeclampsia rats.. Coenzyme Q10 attenuated placental inflammatory and oxidative stress, thereby protecting the rats against preeclampsia by activating the Nrf2/HO-1 pathway.

Topics: Animals; Disease Models, Animal; Female; Heme Oxygenase (Decyclizing); NF-E2-Related Factor 2; Pre-Eclampsia; Pregnancy; Rats; Rats, Sprague-Dawley; Signal Transduction; Ubiquinone

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble antioxidant. Although CoQ10 has not been approved as medication by the Food and Drug Administration, it is widely used in dietary supplements. Some studies have shown that CoQ10 has anti-inflammatory effects on various autoimmune disorders. In this study, we investigated the anti-inflammatory effects of liposome/gold hybrid nanoparticles encoded with CoQ10 (LGNP-CoQ10). Both CoQ10 and LGNP-CoQ10 were administered orally to mice with collagen-induced arthritis (CIA) for 10 weeks. The inflammation pathology of joint tissues of CIA mice was then analyzed using hematoxylin and eosin and Safranin O staining, as well as immunohistochemistry analysis. We obtained immunofluorescence staining images of spleen tissues using confocal microscopy. We found that pro-inflammatory cytokines were significantly decreased in LGNP-CoQ10 injected mice. Th17 cell and phosphorylated STAT3-expressed cell populations were also decreased in LGNP-CoQ10 injected mice. When human peripheral blood mononuclear cells (PBMCs) were treated with CoQ10 and LGNP-CoQ10, the IL-17 expression of PBMCs in the LGNP-CoQ10-treated group was significantly reduced. Together, these results suggest that LGNP-CoQ10 has therapeutic potential for the treatment of rheumatoid arthritis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Arthritis, Rheumatoid; Autoimmune Diseases; Cell Line; Cytokines; Disease Models, Animal; Gold; Humans; Inflammation; Interleukin-17; Leukocytes, Mononuclear; Liposomes; Male; Metal Nanoparticles; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; STAT3 Transcription Factor; T-Lymphocytes, Regulatory; Th17 Cells; Ubiquinone

Sepsis increases the risk of the liver injury development. According to the research works, coenzyme Q10 exhibits hepatoprotective properties in vivo as well as in vitro. Current work aimed at investigating the protective impacts of coenzyme Q10 against liver injury in septic BALB/c mice. The male BALB/c mice were randomly segregated into 4 groups: the control group, the coenzyme Q10 treatment group, the puncture and cecal ligation group, and the coenzyme Q10+cecal ligation and puncture group. Cecal ligation and puncture was conducted after gavagaging the mice with coenzyme Q10 during two weeks. Following 48 h postcecal ligation and puncture, we estimated hepatic biochemical parameters and histopathological changes in hepatic tissue. We evaluated the expression of factors associated with autophagy, pyroptosis, and inflammation. Findings indicated that coenzyme Q10 decreased the plasma levels in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in the cecal ligation and puncture group. Coenzyme Q10 significantly inhibited the elevation of sequestosome-1, interleukin-1

Topics: Alanine Transaminase; Animals; Autophagy; Beclin-1; Body Weight; Disease Models, Animal; Gene Expression Regulation; Immunohistochemistry; Inflammation; Interleukin-6; Liver; Liver Diseases; Male; Mice; Mice, Inbred BALB C; Pyroptosis; Sepsis; Tumor Necrosis Factor-alpha; Ubiquinone; Up-Regulation

We aimed to create mechanic optic nerve injury model in rats and investigate the neuroprotective effects of topical Coenzyme Q10 + Vitamin E (CoQ + Vit.E) molecules on retinal ganglion cells.. Mechanic optic nerve injury model was created in the right eyes of rats (n = 12). Rats were divided into two groups: glaucoma model with sham treatment and topical CoQ + Vit.E treatment. Treatment was applied for 4 weeks. Glial fibrillary acidic protein, Brn-3a antibody, and anti-Iba1 were examined by immunohistochemistry. Glial fibrillary acidic protein, Bax, Bcl-xL, and Tfam protein expression were measured by Western blot analysis.. The number of Brn-3a-positive retinal ganglion cell was 15.0 ± 1.0 (min: 14, max: 16) in sham treatment group and 22.2 ± 4.8 (min: 18, max: 29) in topical CoQ10 + Vit.E treatment group. The protection of Brn-3a in CoQ10 + Vit.E was statistically significant (p < 0.05). Glial fibrillary acidic protein-positive astroglial counts were recorded as 11.7 ± 2.1 (min: 10, max: 14) in sham treatment and 2.5 ± 1.5 (min: 1, max: 4) in topical CoQ10 + Vit.E treatment group (p < 0.05). Topical CoQ10 + Vit.E treatment also decreased Iba1 expression in the retina of mechanic optic nerve injury groups. CoQ10 + Vit.E treatment prevented apoptotic cell death by increasing Bcl-xL protein expression. Also, CoQ10 + Vit.E preserved Tfam protein expression in the retina.. This study has shown that in glaucoma treatment the neuron protecting effect of topical CoQ10 + Vit.E molecules can be valuable.

Topics: Administration, Ophthalmic; Animals; bcl-2-Associated X Protein; bcl-X Protein; Blotting, Western; Calcium-Binding Proteins; Disease Models, Animal; Drug Combinations; Glaucoma; Glial Fibrillary Acidic Protein; Immunohistochemistry; Male; Microfilament Proteins; Neuroprotective Agents; Ophthalmic Solutions; Optic Nerve Injuries; Rats; Rats, Wistar; Retinal Ganglion Cells; Transcription Factor Brn-3A; Ubiquinone; Vitamin E

Spinal cord injury (SCI) has always been considered to be a devastating problem that results in catastrophic dysfunction, high disability rate, low mortality rate, and huge cost for the patient. Stem cell-based therapy, especially using bone marrow mesenchymal stem cells (BMSCs), is a promising strategy for the treatment of SCI. However, SCI results in low rates of cell survival and a poor microenvironment, which limits the therapeutic efficiency of BMSC transplantation. Coenzyme Q10 (CoQ10) is known as a powerful antioxidant, which inhibits lipid peroxidation and scavenges free radicals, and its combined effect with BMSC transplantation has been shown to have a powerful impact on protecting the vitality of cells, as well as antioxidant and antiapoptotic compounds in SCI. Therefore, we aimed to evaluate whether CoQ10 could decrease oxidative stress against the apoptosis of BMSCs

Topics: Animals; Apoptosis; Bone Marrow Cells; Disease Models, Animal; Hydrogen Peroxide; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord Injuries; Ubiquinone

Alzheimer's disease (AD) is the most prevalent form of dementia and is associated with loss of memory, amyloid-beta plaque buildup, and neurofibrillary tangles. These features might be a result of neuronal cell death in the cerebral cortex and hippocampal regions of the brain. AD pathologies can be attributed to a variety of biochemical consequences including mitochondrial dysfunction, increased oxidative stress, and autophagy inhibition. Unfortunately, current therapeutics are limited only to symptomatic relief and do not halt the progression of neurodegeneration. Previous in vitro experiments have shown that a water-soluble formulation of coenzyme-Q

Topics: Alzheimer Disease; Animals; Autophagy; Beclin-1; Cell Death; Cellular Senescence; Cerebral Cortex; Disease Models, Animal; Fibroblasts; Humans; Mice; Mice, Transgenic; Mitogen-Activated Protein Kinase 8; Mutation; Neuroprotection; Presenilin-1; Ubiquinone; Up-Regulation

Glaucoma is a multifactorial neurodegenerative disorder and one of the leading causes of irreversible blindness globally and for which intraocular pressure is the only modifiable risk factor. Although neuroprotective therapies have been suggested to have therapeutic potential, drug delivery for the treatment of ocular disorders such as glaucoma remains an unmet clinical need, further complicated by poor patient compliance with topically applied treatments. In the present study we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating three recognised neuroprotective agents (dexamethasone (DX), melatonin (MEL) and coenzyme Q10 (CoQ10)) in a single formulation (DMQ-MSs) to create a novel sustained-release intraocular drug delivery system (IODDS) for the treatment of glaucoma. MSs were spherical, with a mean particle size of 29.04 ± 1.89 μm rendering them suitable for intravitreal injection using conventional 25G-32G needles. >62% incorporation efficiency was achieved for the three drug cargo and MSs were able to co-deliver the encapsulated active compounds in a sustained manner over 30-days with low burst release. In vitro studies showed DMQ-MSs to be neuroprotective in a glutamate-induced cytotoxicity model (IC

Topics: Animals; Dexamethasone; Disease Models, Animal; Drug Carriers; Drug Compounding; Drug Liberation; Drug Therapy, Combination; Glaucoma; Humans; Injections, Intraocular; Male; Melatonin; Microspheres; Neuroprotective Agents; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Retina; Transcription Factor Brn-3B; Treatment Outcome; Ubiquinone

Oxidative stress plays a key role in contributing to β-amyloid (Aβ) deposition in Alzheimer's disease (AD). Coenzyme Q10 (Q10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals. In this study, we investigated the neuroprotective effects of Q10 on Aβ-induced impairment in hippocampal long-term potentiation (LTP), a widely researched model of synaptic plasticity, which occurs during learning and memory, in a rat model of AD. In this study, 50 adult male Wistar rats were assigned to five groups: control group (saline); sham group; intraventricular PBS injection, Aβ group; intraventricular Aβ injection, Q10 group; and Q10 via oral gavage and Q10 + Aβ group. Q10 was administered via oral gavage, once a day, for 3 weeks before and 3 weeks after the Aβ injection. After the treatment period, in vivo electrophysiological recordings were performed to quantify the excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the hippocampal dentate gyrus. LTP was created by a high-frequency stimulation of the perforant pathway. Following LTP induction, the EPSP slope and PS amplitude were significantly diminished in Aβ-injected rats, compared with sham and control rats. Q10 treatment of Aβ-injected rats significantly attenuated these decreases, suggesting that Q10 reduces the effects of Aβ on LTP. Aβ significantly increased serum malondialdehyde levels and total oxidant levels, whereas Q10 supplementation significantly reversed these parameters and increased total antioxidant capacity levels. The present findings suggested that Q10 treatment offers neuroprotection against the detrimental effects of Aβ on hippocampal synaptic plasticity via its antioxidant activity.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Dentate Gyrus; Disease Models, Animal; Excitatory Postsynaptic Potentials; Hippocampus; Long-Term Potentiation; Male; Memory; Memory Disorders; Neuronal Plasticity; Neuroprotective Agents; Oxidative Stress; Peptide Fragments; Rats; Rats, Wistar; Synaptic Transmission; Temporal Lobe; Ubiquinone

The vast majority of mitochondrial disorders have limited the clinical management to palliative care. Rapamycin has emerged as a potential therapeutic drug for mitochondrial diseases since it has shown therapeutic benefits in a few mouse models of mitochondrial disorders. However, the underlying therapeutic mechanism is unclear, the minimal effective dose needs to be defined and whether this therapy can be generally used is unknown.. We have evaluated whether low and high doses of rapamycin administration may result in therapeutic effects in a mouse model (Coq9. Low dose of rapamycin induces metabolic changes in liver and transcriptomics modifications in midbrain. The high dose of rapamycin induces further changes in the transcriptomics profile in midbrain due to the general inhibition of mTORC1. However, neither low nor high dose of rapamycin were able to improve the mitochondrial bioenergetics, the brain injuries and the phenotypic characteristics of Coq9. These results may be due to the lack of microgliosis-derived neuroinflammation, the limitation to induce autophagy, or the need of a functional CoQ-junction. Therefore, the translation of rapamycin therapy into the clinic for patients with mitochondrial disorders requires, at least, the consideration of the particularities of each mitochondrial disease. FUND: Supported by the grants from "Fundación Isabel Gemio - Federación Española de Enfermedades Neuromusculares - Federación FEDER" (TSR-1), the NIH (P01HD080642) and the ERC (Stg-337327).

Topics: Animals; Autophagy; Cell Respiration; Disease Models, Animal; Gene Expression Profiling; Humans; Metabolomics; Mice; Mitochondria; Mitochondrial Diseases; Mitochondrial Encephalomyopathies; Phenotype; Sirolimus; Treatment Outcome; Ubiquinone

Type 2 diabetic patients possess a two to four fold-increased risk for Cardiovascular Diseases (CVD). Hyperglycemia, oxidative stress associated with endothelial dysfunction and dyslipidemia are regarded as pro-atherogenic mechanisms of CVD. In this study, high-fat diet-induced diabetic and non-diabetic vervet monkeys were treated with 90 mg/kg of aspalathin-rich green rooibos extract (Afriplex GRT) for 28 days, followed by a 1-month wash-out period. Supplementation showed improvements in both the intravenous glucose tolerance test (IVGTT) glycemic area under curve (AUC) and total cholesterol (due to a decrease of the low-density lipoprotein [LDL]) values in diabetics, while non-diabetic monkeys benefited from an increase in high-density lipoprotein (HDL) levels. No variation of plasma coenzyme Q10 (CoQ

Topics: Animals; Biomarkers; Blood Glucose; Chalcones; Chlorocebus aethiops; Cholesterol, LDL; Diabetes Mellitus, Experimental; Diet, High-Fat; Disease Models, Animal; Female; Hypoglycemic Agents; Lipids; Lipoproteins, LDL; Male; Oxidation-Reduction; Oxidative Stress; Plant Extracts; Ubiquinone

Coenzyme Q

Topics: Administration, Oral; Animals; Antioxidants; Biological Availability; Catalepsy; Disease Models, Animal; Emulsions; Female; Male; Microscopy, Electron; Movement; Oxidative Stress; Parkinson Disease; Rats; Rats, Wistar; Refractometry; Solubility; Surface-Active Agents; Swimming; Thiobarbituric Acid Reactive Substances; Ubiquinone; Viscosity

Parkinson's disease (PD) affects ∼1-2% of the elderly population. Development of a neuroprotective therapy that may be initiated early in the course of the disease to retard/prevent disease progression is highly desirable. This study aimed to investigate prophylactic treatment with coenzyme Q10 (CoQ10) before paraquat (PQ) exposure, a herbicide known to increase the risk for PD, to attain neuroprotection. In addition, therapeutic intervention with CoQ10 in mice already exposed to PQ (24 h) might halt ongoing neurodegeneration and behavioural deterioration. PD was induced experimentally in mice by an injection of PQ (10 mg/kg, intraperitoneal), twice a week for 3 consecutive weeks, either before or after the initiation of treatment with CoQ10 (200 mg/kg). The results of the sustained supplementation with CoQ10, prophylactically and therapeutically, were compared with L-DOPA (100 mg/kg). A battery of behavioural tests was performed, in addition to estimation of protein carbonyl in the brain. CoQ10 elicited a remarkable improvement in most of the behavioural tests and decreased protein carbonyl content in the brain, particularly when it was initiated before rather than after PQ induction of PD. Therefore, CoQ10, which protects against mitochondrial damage, may be beneficial in slowing the progression of PD, particularly when initiated as prophylactic treatment.

Topics: Animals; Disease Models, Animal; Levodopa; Male; Mice; Mitochondria; Neurons; Neuroprotective Agents; Oxidative Stress; Paraquat; Parkinson Disease; Protein Carbonylation; Ubiquinone

 Alzheimer's disease (AD) is one of the most common neurodegenerative pathologies for which there are no effective therapies to halt disease progression. Given the increase in the incidence of this disorder, there is an urgent need for pharmacological intervention. Unfortunately, recent clinical trials produced disappointing results. Molecular mechanisms of AD are converging on the notion that mitochondrial dysfunction, oxidative stress, and accumulation of dysfunctional proteins are involved in AD pathology. Previously, we have shown that a water-soluble formulation of Coenzyme Q10 (Ubisol-Q10), an integral part of the electron transport chain, stabilizes mitochondria and prevents neuronal cell death caused by neurotoxins or oxidative stress both in vitro and in vivo. In this study, we evaluated the neuroprotective effects of Ubisol-Q10 treatment in double transgenic AD mice. In the present study, we report that providing Ubisol-Q10 in drinking water (at a dose of ∼6 mg/kg/day) reduced circulating amyloid-β (Aβ) peptide, improved long term memory, preserved working spatial memory, and drastically inhibited Aβ plaque formation in 18-month-old transgenic mice compared to an untreated transgenic group. Thus Ubisol-Q10 supplementation has the potential to inhibit the progression of neurodegeneration, leading to a better quality of life for humans suffering with AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Disease Models, Animal; Male; Maze Learning; Memory; Memory Disorders; Mice; Mice, Transgenic; Microglia; Mutation; Nerve Tissue Proteins; Peptide Fragments; Presenilin-1; Ubiquinone; Vitamins

Primary disorders of the human coenzyme Q

Topics: Animals; Apoptosis; Ataxia; Biosynthetic Pathways; Cytochrome P-450 Enzyme System; Disease Models, Animal; Humans; Hydroxybenzoates; Mice; Mitochondria; Mitochondrial Diseases; Muscle Weakness; Pyrimidines; Solubility; Treatment Outcome; Ubiquinone; Vitamins

Probiotic complex, zinc, and coenzyme Q10 (CoQ10) are recognized dietary supplements with an anti-inflammatory role. Although these supplementations are individually known to benefit rheumatoid arthritis (RA), there is no evidence suggesting any synergic effect. The primary goal of this study is to determine whether probiotic complex, zinc, and CoQ10 attenuate the development of collagen-induced arthritis (CIA). The combination of probiotic complex, zinc, and CoQ10 reduced CIA severity by downregulating the levels of IgG, IgG1, and IgG2a in serum. Joint inflammation, bone destruction, and cartilage damage were also improved by the complex. There was a decrease in the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-17, and vascular endothelial growth factor (VEGF) in the joint synovium. The balance between helper T 17 (Th17) cells and regulatory T (Treg) cells was shown to be controlled reciprocally by the complex. These findings suggest that the combination of probiotic complex, zinc, and CoQ10 can ameliorate the development of CIA by inhibiting the expression of proinflammatory cytokines, and is thus an important therapeutic candidate for RA treatment.

Topics: Animals; Arthritis, Rheumatoid; Disease Models, Animal; Drug Therapy, Combination; Humans; Interleukin-17; Interleukin-6; Male; Mice; Mice, Inbred DBA; Probiotics; T-Lymphocytes, Regulatory; Th17 Cells; Tumor Necrosis Factor-alpha; Ubiquinone; Zinc

Coenzyme Q. Our study confirmed the strong anti-inflammatory effects of coenzyme Q. There is significant synergy between coenzyme Q

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Autoimmune Diseases; Cell Line, Tumor; Cytokines; Disease Models, Animal; Drug Synergism; Female; Glucans; Humans; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Phagocytosis; RAW 264.7 Cells; Ubiquinone

Nitrogen mustard (NM) is a devastating casualty agent in chemical warfare. There is no effective antidote to treat NM-induced ocular injury. We aimed to assess the effects of proanthocyanidin (PAC) and coenzyme Q10 (CoQ10) on NM-induced ocular injury.. Eighteen male rats were divided into the following 4 groups: NM, NM + PAC, NM + CoQ10, and control. The 3 NM groups received a single dose of NM (0.02 mg/μL) on the right eye to induce ocular injury. The control group received saline only. Thirty minutes after the application of NM, the NM + PAC group received PAC (100 mg/kg) via gastric gavage, while the NM + CoQ10 group received CoQ10 (10 mg/kg) via intraperitoneal injection. PAC and CoQ10 were administered once a day for 5 consecutive days. The rats were then sacrificed. Macroscopic images of the eyes were examined and eye tissues were collected for histology.. The treatment groups were compared to the control group with regard to both corneal opacity and lid injury scores. The findings were not significantly different for both the NM + PAC and NM + CoQ10 groups. In both the NM + PAC and NM + CoQ10 groups, the histological changes seen in the NM group demonstrated improvement.. Our results indicate that PAC and CoQ10 treatments have therapeutic effects on NM-induced ocular injury in a rat model. PAC and CoQ10 may be novel options in patients with NM-induced ocular injury.

Topics: Animals; Antioxidants; Burns, Chemical; Chemical Warfare Agents; Disease Models, Animal; Eye Injuries; Male; Mechlorethamine; Proanthocyanidins; Random Allocation; Rats; Rats, Sprague-Dawley; Ubiquinone

Berberine and coenzyme Q10 (CoQ10) are agents with anti-inflammatory and antioxidant characteristics. The purpose of this study was to investigate the effectiveness of berberine and CoQ10 on allergic rhinitis.. This study involved 30 Sprague-Dawley rats, and allergic rhinitis model was established with induction of ovalbumin. Rats were randomized into five groups. The first represented the control group, in which no allergy was established. The second represented the allergy group, in which allergy was induced but no treatment was given. In the remaining three groups, following induction of allergy, desloratadine at a dose of 10 mg/kg was given to Group 3, 100 mg/kg dose of berberine to Group 4, and 20 mg/kg dose of CoQ10 to Group 5. Nasal symptom scores, and plasma immunoglobulin-E, interleukin (IL)-4, IL-13, malondialdehyde (MDA) and nitric oxide (NO) levels were examined at the end of the study. Rats' nasal tissues were also subjected to histopathological immunohistochemical examination.. Nasal symptom scores, and plasma immunoglobulin-E, IL-4, IL-13, MDA and NO levels increased significantly in rats with induced allergic rhinitis. Berberine and CoQ10 significantly reduced these elevated levels. CoQ10 was also found as effective as desloratadin in terms of nasal symptom scores and biochemical parameters. At histopathological examination, severe allergic inflammation was observed in rats from allergic rhinitis group. At all treatment groups, the histopathological changes were significantly improved and only a mild inflammation was determined. Also, immunochemistry showed a significant improvement in all three treatment groups. Coenzyme Q10 and berberine were both effective in suppressing allergy symptoms.. We think that berberine and coenzyme Q10 can usefully be employed as therapy due to their antioxidant and anti-inflammatory effects in an experimentally induced allergic rhinitis model.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Berberine; Disease Models, Animal; Histamine H1 Antagonists, Non-Sedating; Immunoglobulin E; Interleukin-13; Interleukin-4; Loratadine; Malondialdehyde; Nitric Oxide; Random Allocation; Rats, Sprague-Dawley; Rhinitis, Allergic; Ubiquinone

Nephrotic syndrome (NS), a frequent chronic kidney disease in children and young adults, is the most common phenotype associated with primary coenzyme Q

Topics: Alkyl and Aryl Transferases; Animals; Antioxidants; Ataxia; Disease Models, Animal; HeLa Cells; Humans; Hydrogen Sulfide; Kidney; Metabolic Networks and Pathways; Mice; Mice, Transgenic; Mitochondria; Mitochondrial Diseases; Muscle Weakness; Nephrotic Syndrome; Oxidation-Reduction; Oxidative Stress; Oxidoreductases Acting on Sulfur Group Donors; Reactive Oxygen Species; Ubiquinone

Topics: Animals; Autophagy; Blotting, Western; Cell Survival; Disease Models, Animal; Flow Cytometry; Mice; Mitochondria, Muscle; Mitochondrial Diseases; Oxidative Stress; Physical Conditioning, Animal; Ubiquinone

Clinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q

Topics: Alkyl and Aryl Transferases; Alleles; Animals; Autophagy; Cell Line; Cells, Cultured; Disease Models, Animal; Gene Silencing; Humans; Mitochondria; Mitophagy; Nephrotic Syndrome; Organisms, Genetically Modified; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Ubiquinone; Vitamins

Anaesthesia can induce cognitive deficiency in young rodents and monkeys. Mitochondrial dysfunction contributes to the anaesthesia-induced neurotoxicity and neurobehavioural deficits. We therefore assessed the effects of the mitochondrial energy enhancer coenzyme Q 10 (CoQ 10 ) on anaesthesia-induced cognitive deficiency in young mice to investigate the role of mitochondrial dysfunction.. Young mice ( n =134) were randomly assigned into the following four groups: control plus corn oil vehicle (60% oxygen); 3% sevoflurane [2 h daily on postnatal day (P) 6, 7, and 8] plus vehicle; CoQ 10 (50 mg kg -1 ) plus vehicle; or 3% sevoflurane plus CoQ 10 plus vehicle. We determined cognitive function using the Morris water maze at P31-P37. We quantified brain postsynaptic density protein-95, the presynaptic marker synaptophysin, adenosine triphosphate, reactive oxygen species, and mitochondrial membrane potential at P8 and P37.. Coenzyme Q 10 reduced sevoflurane-induced cognitive deficiency in young mice ( F =0.90, P =0.49, n =10-16) and attenuated sevoflurane-induced reductions in postsynaptic density protein-95 ( F =10.56, P <0.01, n =6), synaptophysin ( F =8.44, P =0.01, n =6), adenosine triphosphate ( F =4.34, P =0.05, n =9), and mitochondrial membrane potential ( F =11.43, P <0.01, n =6), but not sevoflurane-induced increases in reactive oxygen species ( F =1.17, P =0.20, n =6), in brain.. These data suggest that CoQ 10 reduces sevoflurane-induced cognitive deficiency by mitigating sevoflurane-induced mitochondrial dysfunction, the reduction in adenosine triphosphate, and synaptic dysfunction. Coenzyme Q 10 could provide an approach to reduce the neurotoxicity of anaesthesia in the developing brain.

Topics: Anesthetics, Inhalation; Animals; Cognition Disorders; Disease Models, Animal; Female; Male; Mice; Mice, Inbred C57BL; Sevoflurane; Ubiquinone; Vitamins

Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier in the mitochondrial respiratory chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to investigate the effects of CoQ10 on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis.. Wistar rats were divided into Sham, CLP, Sham+CoQ10, CLP+CoQ10 subgroups. CoQ10 (10mg/kg/day) or vehicle (olive oil; 1mL/kg/day) was intraperitoneally injected for 15days. At 16th day, Sham or CLP operation was performed. 20h after the operations, MABF and phenylephrine responses of isolated aortic rings were measured. Tissue samples were obtained for histopathological and biochemical evaluations. Furthermore, survival rates were monitored throughout 96h.. CoQ10 prevented mesenteric hypoperfusion and aortic dysfunction induced by CLP. Survival rate was %0 at 46th h in CLP group, but in CLP+CoQ10 group it was 37.5% at the end of 96h. CLP-induced elevations of serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were blocked by CoQ10. CoQ10 restored the increased liver, lung, spleen and kidney malondialdehyde levels and as well as reduced liver and spleen glutathione levels. The protective effects of CoQ10 on multiple organ damage were also observed histopathologically.. CoQ10 showed protective effects in sepsis due to its preservative effects on mesenteric perfusion, aortic function and also its anti-inflammatory and antioxidative effects.

Topics: Animals; Aorta; Cecum; Cytokines; Disease Models, Animal; Female; Inflammation; Ligation; Malondialdehyde; Mesenteric Ischemia; Protective Agents; Rats; Rats, Wistar; Renal Circulation; Sepsis; Survival Rate; Ubiquinone

Coenzyme Q10 (CoQ10) is a mitochondrial-targeted antioxidant with known neuroprotective activity. Its ocular effects when co-solubilised with α-tocopherol polyethylene glycol succinate (TPGS) were evaluated. In vitro studies confirmed that CoQ10 was significantly protective in different retinal ganglion cell (RGC) models. In vivo studies in Adult Dark Agouti (DA) rats with unilateral surgically-induced ocular hypertension (OHT) treated with either CoQ10/TPGS micelles or TPGS vehicle twice daily for three weeks were performed, following which retinal cell health was assessed in vivo using DARC (Detection of Apoptotic Retinal Cells) and post-mortem with Brn3a histological assessment on whole retinal mounts. CoQ10/TPGS showed a significant neuroprotective effect compared to control with DARC (p<0.05) and Brn3 (p<0.01). Topical CoQ10 appears an effective therapy preventing RGC apoptosis and loss in glaucoma-related models.

Topics: Animals; Disease Models, Animal; Male; Mitochondria; Neuroprotection; Neuroprotective Agents; Ocular Hypertension; Rats; Retinal Ganglion Cells; Treatment Outcome; Ubiquinone; Vitamin E

Coenzyme Q10 (CoQ10) is a powerful antioxidant substance synthesized in the body. The current study aimed to determine whether CoQ10 suppresses inflammation and inhibits p-STAT3 expression in an experimental colitis mouse model. The mice were orally fed with CoQ10 once a day for 13 days. Histological analysis of the colons was performed by immunohistochemistry. Expression of IL-17, FOXP3, p53, AMPK, and mTOR and activation of p-STAT3 and p-STAT5 in lymph node and spleen tissues were detected by confocal microscopy of stained tissue sections. The relative mRNA expression was measured with real-time PCR, and protein levels were examined by western blot. CoQ10 reduced the disease activity index score and the colon histological score. It also reduced inflammatory mediators in the colon and increased the colon length. The expression of IL-17 and p-STAT3 was decreased with CoQ10 treatment. In contrast, CoQ10 treatment increased the expression of p-AMPK and FOXP3. Expression of anti-inflammatory cytokines was shown to increase in colitis mice treated with CoQ10. These results suggested that CoQ10 may reduce the severity of colitis and suppress inflammation through the inhibition of p-STAT3 and IL-17. These results support the use of CoQ10 as a potential targeted therapy for the treatment of colitis.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Disease Models, Animal; Humans; Interleukin-17; Male; Mice; Mice, Inbred C57BL; STAT3 Transcription Factor; Th17 Cells; Ubiquinone

The purpose of this study was to compare the effects of thymoquinone and icodextrin in rats within the framework of an experimental adhesion model.. Rats were separated into three groups: (1) a control group consisting of rats that had 2 ml of isotonic solution administered intraperitoneally, (2) an ICO group administered with 2 ml of 4% icodextrin, and (3) a TQ group administered thymoquinone (10 mg/kg), all following cecal abrasion. The three groups underwent a reoperation on the 7th postoperative day. Hydroxyproline levels were analyzed in the resected adhesive tissues, and histopathological investigations were conducted. Blood samples were collected for biochemical analyses.. Fewer postoperative adhesions were observed in the ICO and TQ groups compared with the control group. A comparison of the TQ and ICO groups revealed lowers levels of postoperative adhesions in the TQ group. Compared with the control group, malondialdehyde, 8-OH-deoxyguanosine/deoxyguanosine (8-OHdG/10dG), Coenzyme Q10 (CoQ10), and CoenzymeQ10/reduced CoenzymeQ10 (CoQ10/CoQ10H) values were found to be lower in the TQ and ICO groups. When the TQ and ICO groups were compared with respect to their biochemical parameters, the results for all of the four parameters were found to be statistically significantly lower in the TQ group (P < 0.000). The levels of hydroxyproline in the control, ICO, and TQ groups were found to be (mean ± standard deviation) 502.25 ± 90.39 μg/g, 342.13 ± 66.61 μg/g, and 287.88 ± 49.59 μg/g, respectively.. A comparison of the antiadhesive effects of thymoquinone and icodextrin revealed thymoquinone to be more effective. These results indicate that thymoquinone is an efficient and strong antiadhesive molecule.

Topics: Animals; Benzoquinones; Disease Models, Animal; Glucans; Glucose; Humans; Icodextrin; Injections, Intraperitoneal; Male; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions; Ubiquinone

An age-dependent model of the periodontium was reproduced to evaluate the effect of life-long feeding on a low coenzyme Q10 dosage in n-6, n-3 polyunsaturated fatty acid or monounsaturated fatty acid-based diets on periodontal tissues of young and old rats. Results shown that exacerbated age-related alveolar bone loss previously associated to n-6 polyunsaturated fatty acid diet was attenuated by coenzyme Q10 Gene expression analysis suggests that involved mechanisms might be related to a restored capacity of mitochondria to adapt to aging in gingival cells from rats fed on n-6 polyunsaturated fatty acid. In particular, this could be due to an age-related increase of the rate of mitochondrial biogenesis and a better oxidative and respiratory balance in these animals. From the nutritional and clinical point of view, it is noteworthy that supplementation with coenzyme Q10 could counteract the negative effects of n-6 polyunsaturated fatty acid on alveolar bone loss (a major feature of periodontitis) associated to age.

Topics: Alveolar Bone Loss; Animals; Diet; Disease Models, Animal; Fatty Acids, Omega-6; Male; Osteoporosis; Rats; Rats, Wistar; Ubiquinone; Vitamins

Doxorubicin (DXR) extravasation result with serious morbidity like skin ulceration and necrosis. The purpose of this study is to determine the protective effects of ozone, olive oil, dimethyl sulfoxide (DMSO), and coenzyme Q10 in the treatment of DXR-induced skin ulcers on rats. After an intradermal injection of DXR on a basis of an animal extravasation model, the materials were topically applied. The ulcer sizes were measured, and a punch biopsy was taken from the extravasation site in which the skin ulcers formed at the end of the experiment. The samples were analyzed for tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL1β), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) enzymes, and examined histopathologically. The ulcer sizes clearly decreased in the study groups, including DMSO, olive oil, ozone plus coenzyme Q10, and ozone plus olive oil groups in comparison with the control group with the exception of the coenzyme Q10 group. The malondialdehyde levels were lower in the DMSO, olive oil, ozone plus olive oil, and ozone plus coenzyme Q10 groups than they were in the control group, but they were not significantly different. The TNF-α level was lower in the DMSO, ozone plus olive oil, coenzyme Q10, and ozone plus coenzyme Q10 groups in comparison with the control group. There was no significant change in the SOD, GSH-Px, and IL1β levels in the study groups in comparison with the control and the sham groups. The ozone plus olive oil group could be considered to be an alternate therapy for skin ulcers due to DXR extravasation.

Topics: Animals; Antibiotics, Antineoplastic; Antioxidants; Biopsy; Dimethyl Sulfoxide; Disease Models, Animal; Doxorubicin; Extravasation of Diagnostic and Therapeutic Materials; Necrosis; Olive Oil; Oxidative Stress; Ozone; Rats; Skin; Skin Ulcer; Ubiquinone

Anti-oxidant coenzyme Q10 (Co-Q10) is commonly used in clinic. Recently, Co-Q10 was reported to antagonize TNF-α-induced inflammation and play a protective role in various inflammatory conditions. However, its role in dermatitis is unknown. Herein, RAW264.7 macrophage cell line was cultured with stimulation of TNF-α, and administration of Co-Q10 alleviated TNF-α-mediated inflammatory reaction in vitro. Furthermore, oxazolone-induced dermatitis mice model was established, and treatment of Co-Q10 markedly attenuated dermatitis phenotype in this mice model. Moreover, the protective role of Co-Q10 in vitro and in dermatitis was probably due to its repression on NF-κB signaling. Collectively, Co-Q10 may represent a potential molecular target for prevention and treatment of inflammatory skin diseases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Line; Dermatitis, Contact; Disease Models, Animal; Inflammation; Interleukin-1beta; Interleukin-6; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Oxazolone; Skin; Tumor Necrosis Factor-alpha; Ubiquinone

HMG-CoA reductase inhibitors (statins) and H63D HFE polymorphism may modify amyotrophic lateral sclerosis (ALS). We hypothesized that statins worsen phenotype in ALS mice, dependent on HFE genotype.. Mice harboring SOD1(G93A) heterozygous for H67D Hfe (homologous to human H63D HFE) were administered simvastatin and/or coenzyme Q10, and were allowed to reach end stage. Disease progression was measured by grip strength. A separate group of animals was administered simvastatin and euthanized at the symptomatic 120-day time-point. Mitochondria from gastrocnemius muscle and lumbar spine were analyzed.. Simvastatin and H67D Hfe accelerated disease progression. Simvastatin decreased survival. Coenzyme Q10 did not rescue statin-induced effects. Statins did not alter mitochondrial protein levels.. Statins and Hfe genotype alter disease course in the ALS mouse model. Because the H63D HFE polymorphism is present in 30% of patients with ALS, studying disease progression in patients who receive statins, stratified for HFE genotype, may guide therapy. Muscle Nerve, 2016 Muscle Nerve 54: 284-291, 2016.

Topics: Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Disease Progression; Extremities; Ferritins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mice; Mice, Transgenic; Mitochondria; Motor Activity; Muscle Strength; Muscle, Skeletal; ROC Curve; Spinal Cord; Superoxide Dismutase; Ubiquinone

Diabetic neuropathic pain is reduced with tight glycemic control. However, strict control increases the risk of hypoglycemic episodes, which are themselves linked to painful neuropathy. This study explored the effects of hypoglycemia-related painful neuropathy. Pretreatment with coenzyme Q10 (CoQ10) was performed to explore the preventive effect of CoQ10 on hypoglycemia-related acute neuropathic pain. Two strains of mice were used and 1 unit/kg of insulin was given to induce hypoglycemia. Mechanical sensitivity of hindpaw withdrawal thresholds was measured using von Frey filaments. Blood glucose levels were clamped at normal levels by joint insulin and glucose injection to test whether insulin itself induced hypersensitivity. Results suggest that the increased mechanical sensitivity after insulin injection is related to decreased blood glucose levels. When blood glucose levels remained at a normal level by the linked administration of insulin and glucose, mice demonstrated no significant change in mechanical sensitivity. Pretreatment with CoQ10 prevented neuropathic pain and the expression of the stress factor c-Fos. These results support the concept that pain in the diabetic scenario can be the result of hypoglycemia and not insulin itself. Additionally, pretreatment with CoQ10 may be a potent preventive method for the development of neuropathic pain.

Topics: Acute Disease; Analgesics; Animals; Biomarkers; Blood Glucose; Disease Models, Animal; Hyperalgesia; Hypoglycemia; Insulin; Mice, Inbred C57BL; Mice, Inbred CBA; Neuralgia; Pain Threshold; Proto-Oncogene Proteins c-fos; Spinal Cord; Time Factors; Ubiquinone

Aspergillus fumigatus is the predominant airborne pathogenic fungus causing invasive aspergillosis in immunocompromised patients. During infection A. fumigatus has to adapt to oxygen-limiting conditions in inflammatory or necrotic tissue. Previously, we identified a mitochondrial protein to be highly up-regulated during hypoxic adaptation. Here, this protein was found to represent the novel oxidoreductase HorA. In Saccharomyces cerevisiae a homologue was shown to play a role in biosynthesis of coenzyme Q. Consistently, reduced coenzyme Q content in the generated ΔhorA mutant indicated a respective function in A. fumigatus. Since coenzyme Q is involved in cellular respiration and maintaining cellular redox homeostasis, the strain ΔhorA displayed an impaired response to both oxidative and reductive stress, a delay in germination and an accumulation of NADH. Moreover, an increased resistance against antifungal drugs was observed. All phenotypes were completely reversed by the addition of the synthetic electron carrier menadione. The deletion strain ΔhorA showed significantly attenuated virulence in two murine infection models of invasive pulmonary aspergillosis. Therefore, the biosynthesis of coenzyme Q and, particularly, the fungal-specific protein HorA play a crucial role in virulence of A. fumigatus. Due to its absence in mammals, HorA might represent a novel therapeutic target against fungal infections.

Topics: Animals; Antifungal Agents; Aspergillus fumigatus; Azoles; Cell Hypoxia; Disease Models, Animal; Female; Fungal Proteins; Gene Deletion; Invasive Pulmonary Aspergillosis; Mice; Oxidoreductases; Ubiquinone; Virulence

There is conflicting clinical evidence whether administration of coenzyme Q10 (CoQ10) improves function following coronary artery bypass graft surgery (CABG). Using a swine model of hibernating myocardium, we tested whether daily CoQ10 would improve contractile function by MRI at 4-week post-CABG. Twelve pigs underwent a thoracotomy and had a constrictor placed on the left anterior descending (LAD). At 12 weeks, they underwent off-pump bypass and received daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo. At 4-week post-CABG, circumferential strain measurements in the hibernating LAD region from placebo and CoQ10 groups were not different and increased to a similar extent with dobutamine (-14.7 ± 0.6 versus -14.8 ± 0.1, respectively (NS)). Post-sacrifice, oxidant stress markers were obtained in the mitochondrial isolates and protein carbonyl in the placebo, and CoQ10 groups were 6.14 ± 0.36 and 5.05 ± 0.32 nmol/mg, respectively (NS). In summary, CoQ10 did not improve contractile reserve or reduce oxidant stress at 4-week post-CABG.

Topics: Animals; Biomarkers; Biomechanical Phenomena; Cardiotonic Agents; Coronary Artery Bypass, Off-Pump; Coronary Artery Disease; Disease Models, Animal; Female; Magnetic Resonance Imaging; Mitochondria, Heart; Myocardial Contraction; Myocardial Stunning; Myocardium; Oxidative Stress; Protein Carbonylation; Recovery of Function; Stress, Mechanical; Sus scrofa; Time Factors; Ubiquinone

Myopathy is among the well documented and the most disturbing adverse effects of statins. The underlying mechanism is still unknown. Mitochondrial dysfunction related to coenzyme Q10 decline is one of the proposed theories. The present study aimed to investigate the mechanism of atorvastatin-induced myopathy in rats. In addition, the mechanism of the coenzyme Q10 protection was investigated with special focus of mitochondrial alterations. Sprague-Dawely rats were treated orally either with atorvastatin (100mg/kg) or atorvastatin and coenzyme Q10 (100mg/kg). Myopathy was assessed by measuring serum creatine kinase (CK) and myoglobin levels together with examination of necrosis in type IIB fiber muscles. Mitochondrial dysfunction was evaluated by measuring muscle lactate/pyruvate ratio, ATP level, pAkt as well as mitochondrial ultrastructure examination. Atorvastatin treatment resulted in a rise in both CK (2X) and myoglobin (6X) level with graded degrees of muscle necrosis. Biochemical determinations showed prominent increase in lactate/pyruvate ratio and a decline in both ATP (>80%) and pAkt (>50%) levels. Ultrastructure examination showed mitochondrial swelling with disrupted organelle membrane. Co-treatment with coenzyme Q10 induced reduction in muscle necrosis as well as in CK and myoglobin levels. In addition, coenzyme Q10 improved all mitochondrial dysfunction parameters including mitochondrial swelling and disruption. These results presented a model for atorvastatin-induced myopathy in rats and proved that mitochondrial dysfunction is the main contributor in statin-myopathy pathophysiology.

Topics: Adenosine Triphosphate; Animals; Atorvastatin; Creatine Kinase; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; L-Lactate Dehydrogenase; Lactic Acid; Male; Microscopy, Electron, Transmission; Mitochondria, Muscle; Motor Activity; Muscle, Skeletal; Muscular Diseases; Myoglobin; Pyruvic Acid; Rats; Rats, Sprague-Dawley; Ubiquinone

The neuroprotective effect of ubiquinone (coenzyme Q10)was demonstrated on the rats model of ischemic stroke provoked by persistent 24-h occlusion of the middle cerebral artery. Coenzyme Q10 (30 mg/kg) was injected intravenously in 60 min after artery occlusion. Ubiquinone crossed the blood-brain barrier, accumulated in the brain, and produced a neuroprotective effect: it alleviated ischemia-induced neurological deficit and reduced the size of necrotic zone by 49% in comparison with rats receiving physiological saline.

Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Free Radical Scavengers; Infarction, Middle Cerebral Artery; Injections, Intravenous; Male; Neuroprotective Agents; Rats, Wistar; Ubiquinone

Does supplementation with co-enzyme Q10 (CoQ10) improve the oocyte mitochondrial abnormalities associated with obesity in mice?. In an obese mouse model, CoQ10 improves the mitochondrial function of oocytes.. Obesity impairs oocyte quality. Oocytes from mice fed a high-fat/high-sugar (HF/HS) diet have abnormalities in mitochondrial distribution and function and in meiotic progression.. Mice were randomly assigned to a normal, chow diet or an isocaloric HF/HS diet for 12 weeks. After 6 weeks on the diet, half of the mice receiving a normal diet and half of the mice receiving a HF/HS diet were randomly assigned to receive CoQ10 supplementation injections for the remaining 6 weeks.. Dietary intervention was initiated on C57Bl6 female mice at 4 weeks of age, CoQ10 versus vehicle injections were assigned at 10 weeks, and assays were conducted at 16 weeks of age. Mice were super-ovulated, and oocytes were collected and stained to assess mitochondrial distribution, quantify reactive oxygen species (ROS), assess meiotic spindle formation, and measure metabolites. In vitro fertilization was performed, and blastocyst embryos were transferred into control mice. Oocyte number, fertilization rate, blastulation rate and implantation rate were compared between the four cohorts. Bivariate statistics were performed appropriately.. HF/HS mice weighed significantly more than normal diet mice (29 versus 22 g, P< 0.001). CoQ10 supplementation did not influence weight. Levels of ATP, citrate, and phosphocreatine were lower and ROS levels were higher in HF/HS mice than in controls (P< 0.001). CoQ10 supplementation significantly increased the levels of metabolites and decreased ROS levels in oocytes from normal diet mice but not in oocytes from HF/HS mice. However, CoQ10 completely prevented the mitochondrial distribution abnormalities observed in the HF/HS mice. Overall, CoQ10 supplementation significantly increased the percentage of normal spindle and chromosome alignment (92.3 versus 80.2%, P= 0.039). In the sub-analysis by diet, the difference did not reach statistical significance. When undergoing IVF, there were no statistically significant differences in the number of mature oocytes, the fertilization rate, blastocyst formation rates, implantation rates, resorption rates or litter size between HF/HS mice receiving CoQ10 or vehicle injections.. Experiments were limited to one species and strain of mice. The majority of experiments were performed after ovulation induction, which may not represent natural cycle fertility.. Improvement in oocyte mitochondrial distribution and function of normal, chow-fed mice and HF/HS-fed mice demonstrates the importance of CoQ10 and the efficiency of the mitochondrial respiratory chain in oocyte competence. Clinical studies are now needed to evaluate the therapeutic potential of CoQ10 in women's reproductive health.. C.E.B. received support from the National Research Training Program in Reproductive Medicine sponsored by the National Institute of Health (T32 HD040135-13) and the Scientific Advisory Board of Vivere Health. K.H.M received support from the American Diabetes Association and the National Institute of Health (R01 HD083895). There are no conflicts of interest to declare.. This study is not a clinical trial.

Topics: Animals; Body Weight; Diet, High-Fat; Disease Models, Animal; Female; Mice; Mitochondria; Obesity; Oocytes; Reactive Oxygen Species; Treatment Outcome; Ubiquinone

Spinal cord ischemia remains a serious complication of thoracoabdominal aortic aneurysm surgery. Coenzyme Q10, a potent antioxidant, has been reported to exert a neuroprotective effect. In the present study, we evaluated the effect of coenzyme Q10 pretreatment on spinal cord ischemia-reperfusion injury.. Male Sprague-Dawley rats were treated with either 300 mg/kg coenzyme Q10 (CoQ10 group, n = 12) or saline (control and sham groups, n = 12 for each group) for 5 days before ischemia. Spinal cord ischemia was induced in the control and CoQ10 groups. Neurological function was assessed using the Basso-Beattie-Bresnahan (BBB) motor rating scale until 7 days after reperfusion, and then the spinal cord was harvested for histopathological examinations and an evaluation of malondialdehyde level.. On post-reperfusion Day 1, the CoQ10 group showed higher BBB scores compared with those in the control group, although the difference was not significant. However, on Day 2, the CoQ10 group showed a significantly higher BBB score than the control group (14.0 [10.3-15.0] vs 8.0 [5.0-9.8], median [IQR], respectively; p = 0.021), and this trend was maintained until Day 7 (17.5 [16.0-18.0] vs 9.0 [6.5-12.8], respectively; p < 0.001). Compared with the control group, the CoQ10 group had more normal motor neurons (p = 0.003), fewer apoptotic changes (p = 0.003) and a lower level of tissue malondialdehyde (p = 0.024).. Pretreatment with 300 mg/kg coenzyme Q10 resulted in significantly improved neurological function and preservation of more normal motor neurons.

Topics: Animals; Disease Models, Animal; Neurologic Examination; Premedication; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Spinal Cord; Ubiquinone

Ulcerative colitis is a chronic inflammatory bowel disease. Recent studies reported a pivotal role of elevated intracellular calcium in this disorder. Coenzyme Q10 (CoQ10) and amlodipine are known to maintain cellular energy, decrease intracellular calcium concentration in addition to their antioxidant and anti-inflammatory properties.. The aim of this study was to evaluate the possible protective effects of CoQ10, amlodipine and their combination on ulcerative colitis.. Colitis was induced in rats by intracolonic injection of 3% acetic acid. CoQ10 (10 mg/kg), amlodipine (3 mg/kg) and their combination were administered for 8 consecutive days before induction of colitis.. Our results showed that administration of CoQ10, amlodipine and their combination decreased colon tissue malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E2 (PGE2), myeloperoxidase (MPO) and heat shock protein (HSP70) levels induced by intracolonic injection of acetic acid and restored many of the colon structure in histological examination. On the other hand, they increased superoxide dismutase (SOD) activity, adenosine-5'-triphosphate (ATP) and interleukin-10 (IL-10) colonic contents.. Administration of either CoQ10 or amlodipine was found to protect against acetic acid-induced colitis. Moreover, their combination was more effective than individual administration of either of them. The protective effect of CoQ10 and amlodipine may be in part via their antioxidant, anti-inflammatory and energy restoration properties.

Topics: Amlodipine; Animals; Anti-Inflammatory Agents; Antioxidants; Colitis, Ulcerative; Colon; Dinoprostone; Disease Models, Animal; Energy Metabolism; Interleukin-1beta; Male; Malondialdehyde; Peroxidase; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Ubiquinone

Diabetes-induced cardiac complications include left ventricular (LV) dysfunction and heart failure. We previously demonstrated that LV phosphoinositide 3-kinase p110α (PI3K) protects the heart against diabetic cardiomyopathy, associated with reduced NADPH oxidase expression and activity. Conversely, in dominant negative PI3K(p110α) transgenic mice (dnPI3K), reduced cardiac PI3K signaling exaggerated diabetes-induced cardiomyopathy, associated with upregulated NADPH oxidase. The goal was to examine whether chronic supplementation with the antioxidant coenzyme Q(10) (CoQ(10)) could attenuate LV superoxide and diabetic cardiomyopathy in a setting of impaired PI3K signaling. Diabetes was induced in 6-week-old nontransgenic and dnPI3K male mice via streptozotocin. After 4 weeks of diabetes, CoQ(10) supplementation commenced (10 mg/kg ip, 3 times/week, 8 weeks). At study end (12 weeks of diabetes), markers of LV function, cardiomyocyte hypertrophy, collagen deposition, NADPH oxidase, oxidative stress (3-nitrotyrosine), and concentrations of CoQ(9) and CoQ(10) were determined. LV NADPH oxidase (Nox2 gene expression and activity, and lucigenin-enhanced chemiluminescence), as well as oxidative stress, were increased by diabetes, exaggerated in diabetic dnPI3K mice, and attenuated by CoQ(10). Diabetes-induced LV diastolic dysfunction (prolonged deceleration time, elevated end-diastolic pressure, impaired E/A ratio), cardiomyocyte hypertrophy and fibrosis, expression of atrial natriuretic peptide, connective tissue growth factor, and β-myosin heavy chain were all attenuated by CoQ(10). Chronic CoQ(10) supplementation attenuates aspects of diabetic cardiomyopathy, even in a setting of reduced cardiac PI3K protective signaling. Given that CoQ(10) supplementation has been suggested to have positive outcomes in heart failure patients, chronic CoQ(10) supplementation may be an attractive adjunct therapy for diabetic heart failure.

Topics: Animals; Antioxidants; Class I Phosphatidylinositol 3-Kinases; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Disease Models, Animal; Humans; Male; Mice; Mice, Transgenic; NADPH Oxidases; Oxidative Stress; Phosphatidylinositol 3-Kinases; Signal Transduction; Ubiquinone; Ventricular Dysfunction, Left

Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant synthesized in human body. This enzyme promotes immune system function and can be used as a dietary supplement. Rheumatoid arthritis (RA) is an autoimmune disease leading to chronic joint inflammation. RA results in severe destruction of cartilage and disability. This study aimed to investigate the effect of CoQ10 on inflammation and Th17 cell proliferation on an experimental rheumatoid arthritis (RA) mice model. CoQ10 or cotton seed oil as control was orally administrated once a day for seven weeks to mice with zymosan-induced arthritis (ZIA). Histological analysis of the joints was conducted using immunohistochemistry. Germinal center (GC) B cells, Th17 cells and Treg cells of the spleen tissue were examined by confocal microscopy staining. mRNA expression was measured by real-time PCR and protein levels were estimated by enzyme-linked immunosorbent assay (ELISA). Flow cytometric analysis (FACS) was used to evaluate Th17 cells and Treg cells. CoQ10 mitigated the severity of ZIA and decreased serum immunoglobulin concentrations. CoQ10 also reduced RANKL-induced osteoclastogenesis, inflammatory mediators and oxidant factors. Th17/Treg axis was reciprocally controlled by CoQ10 treatment. Moreover, CoQ10 treatment on normal mouse and human cells cultured in Th17 conditions decreased the number of Th17 cells and enhanced the number of Treg cells. CoQ10 alleviates arthritis in mice with ZIA declining inflammation, Th17 cells and osteoclast differentiation. These findings suggest that CoQ10 can be a potential therapeutic substance for RA.

Topics: Animals; Arthritis, Experimental; Autoantibodies; Autoimmune Diseases; B-Lymphocytes; Bone Resorption; Cell Differentiation; Disease Models, Animal; Germinal Center; Humans; Immunophenotyping; Immunosuppressive Agents; Interleukin-17; Leukocytes, Mononuclear; Mice; Osteoclasts; Spleen; T-Lymphocyte Subsets; Th17 Cells; Ubiquinone; Zymosan

Cardioprotective efficacy of coenzyme Q10 (CoQ10, ubidecarenone) and mexicor were evaluated on the 21st day of experimental myocardial infarction in Wistar rats. CoQ10 or mexicor were injected in a dose of 30 mg/kg intravenously 10 min after coronary artery occlusion. The observed cardioprotective effects of ubidecarenone and mexicor were close. Both drugs equally increased the survival of rats, prevented the development of dilatation and hypertrophy of the left ventricle, and improved the pump cardiac function.

Topics: Animals; Cardiotonic Agents; Disease Models, Animal; Male; Myocardial Infarction; Pyridines; Rats; Rats, Wistar; Ubiquinone; Vitamins

Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of cholesterol biosynthesis characterized by diminished cholesterol and increased 7-dehydrocholesterol (7-DHC) levels. 7-Dehydrocholesterol is highly reactive, giving rise to biologically active oxysterols.. 7-DHC-derived oxysterols were measured in fibroblasts from SLOS patients and an in vivo SLOS rodent model using high-performance liquid chromatography tandem mass spectrometry. Expression of lipid biosynthesis genes was ascertained by quantitative polymerase chain reaction and Western blot. The effects of an antioxidant mixture of vitamin A, coenzyme Q10, vitamin C, and vitamin E were evaluated for their potential to reduce formation of 7-DHC oxysterols in fibroblast from SLOS patients. Finally, the effect of maternal feeding of vitamin E enriched diet was ascertained in the brain and liver of newborn SLOS mice.. In cultured human SLOS fibroblasts, the antioxidant mixture led to decreased levels of the 7-DHC-derived oxysterol, 3β,5α-dihydroxycholest-7-en-6-one. Furthermore, gene expression changes in SLOS human fibroblasts were normalized with antioxidant treatment. The active ingredient appeared to be vitamin E, as even at low concentrations, it significantly decreased 3β,5α-dihydroxycholest-7-en-6-one levels. In addition, analyzing a mouse SLOS model revealed that feeding a vitamin E enriched diet to pregnant female mice led to a decrease in oxysterol formation in brain and liver tissues of the newborn Dhcr7-knockout pups.. Considering the adverse effects of 7-DHC-derived oxysterols in neuronal and glial cultures and the positive effects of antioxidants in patient cell cultures and the transgenic mouse model, we believe that preventing formation of 7-DHC oxysterols is critical for countering the detrimental effects of DHCR7 mutations.

Topics: alpha-Tocopherol; Animals; Animals, Newborn; Antioxidants; Ascorbic Acid; Brain; Cell Line, Transformed; Disease Models, Animal; Female; Fibroblasts; Gene Expression Regulation; Humans; Liver; Male; Mice; Mice, Transgenic; Oxidoreductases Acting on CH-CH Group Donors; Smith-Lemli-Opitz Syndrome; Ubiquinone

It is estimated that one-third of infertility cases are due to male factors. Hyper-cholesterolemia is a social problem in many developed countries and contributed with a heterogeneous group of disorders characterized by an excess of cholesterol and its derivatives in the blood stream.. The objective of the present study was to investigate the protective effects of coenzyme Q10 and L-Carnitine supplementation on semen parameters, sperm function and reproductive hormone profiles in male Wistar rats with high LDL and Oxidized LDL (OxLDL) blood levels.. Animals were fed with cholesterol and oxidized cholesterol-rich diets for 14 weeks to elevate the LDL and OxLDL blood level, respectively. Pretreatment with coenzyme Q10 (10 mg/kg/day, oral) and L-Carnitine (350 mg/kg/day, oral) were conducted for 5 consecutive weeks. Sex hormones levels, malondialdehyde and total antioxidant concentrations, as well as testis, epididymis and seminal vesicle weight were also analyzed.. Following high LDL and OxLDL blood levels, decrease in the sperms count and viability, weights of testis, epididymis and seminal vesicle as well as concentration of testosterone and LH hormone were observed. On the other hand, in contrast to reduction of total antioxidant level, malondialdehyde concentration, both in serum and testis, was increased. However, pretreatment with L-carnitine and coenzyme Q10 increased serum sex hormones level and improved semen parameters significantly.. Overall, pretreatment with coenzyme Q10 and L-Carnitine attenuated the destructive effects of high LDL and oxidized LDL levels on spermatogenesis parameters in male rats.

Topics: Animals; Antioxidants; Carnitine; Cell Survival; Cholesterol, Dietary; Cytoprotection; Disease Models, Animal; Epididymis; Hypercholesterolemia; Infertility, Male; Lipoproteins, LDL; Luteinizing Hormone; Male; Malondialdehyde; Rats, Wistar; Sperm Count; Sperm Motility; Spermatogenesis; Spermatozoa; Testis; Testosterone; Ubiquinone

To test whether a diet supplemented with coenzyme Q10 (CoQ10) ameliorates glutamate excitotoxicity and oxidative stress-mediated retinal ganglion cell (RGC) degeneration by preventing mitochondrial alterations in the retina of glaucomatous DBA/2J mice.. Preglaucomatous DBA/2J and age-matched control DBA/2J-Gpnmb(+) mice were fed with CoQ10 (1%) or a control diet daily for 6 months. The RGC survival and axon preservation were measured by Brn3a and neurofilament immunohistochemistry and by conventional transmission electron microscopy. Glial fibrillary acidic protein (GFAP), superoxide dismutase-2 (SOD2), heme oxygenase-1 (HO1), N-methyl-d-aspartate receptor (NR) 1 and 2A, and Bax and phosphorylated Bad (pBad) protein expression was measured by Western blot analysis. Apoptotic cell death was assessed by TUNEL staining. Mitochondrial DNA (mtDNA) content and mitochondrial transcription factor A (Tfam)/oxidative phosphorylation (OXPHOS) complex IV protein expression were measured by real-time PCR and Western blot analysis.. Coenzyme Q10 promoted RGC survival by approximately 29% and preserved the axons in the optic nerve head (ONH), as well as inhibited astroglial activation by decreasing GFAP expression in the retina and ONH of glaucomatous DBA/2J mice. Intriguingly, CoQ10 significantly blocked the upregulation of NR1 and NR2A, as well as of SOD2 and HO1 protein expression in the retina of glaucomatous DBA/2J mice. In addition, CoQ10 significantly prevented apoptotic cell death by decreasing Bax protein expression or by increasing pBad protein expression. More importantly, CoQ10 preserved mtDNA content and Tfam/OXPHOS complex IV protein expression in the retina of glaucomatous DBA/2J mice.. Our findings suggest that CoQ10 may be a promising therapeutic strategy for ameliorating glutamate excitotoxicity and oxidative stress in glaucomatous neurodegeneration.

Topics: Animals; Axons; bcl-Associated Death Protein; Blotting, Western; Disease Models, Animal; Female; Glaucoma; Glial Fibrillary Acidic Protein; Glutamic Acid; Heme Oxygenase-1; In Situ Nick-End Labeling; Membrane Proteins; Mice; Mice, Inbred DBA; Mitochondria; Nerve Tissue Proteins; Oxidative Stress; Real-Time Polymerase Chain Reaction; Receptors, N-Methyl-D-Aspartate; Retinal Degeneration; Retinal Ganglion Cells; Superoxide Dismutase; Ubiquinone; Vitamins

Alzheimer's disease (AD) is the most common fatal neurodegenerative disease affecting the elderly worldwide. There is an urgent need to identify novel biomarkers of early AD. This study aims to search for potential early protein biomarkers in serum from a triple transgenic (PS1M146V/APPSwe/TauP301L) mouse model. Proteomic analysis via two-dimensional fluorescence difference gel electrophoresis was performed on serum samples from wild-type (WT) and triple transgenic mice that were treated with or without coenzyme Q10 (CoQ10) (800 mg/kg body weight/day), a powerful endogenous antioxidant displaying therapeutic benefits against AD pathology and cognitive impairment in multiple AD mouse models, for a period of three months beginning at two months of age. A total of 15 differentially expressed serum proteins were identified between the WT and AD transgenic mice. The administration of CoQ10 was found to alter the changes in the differentially expressed serum proteins by upregulating 10 proteins and down-regulating 10 proteins. Among the proteins modulated by CoQ10, clusterin and α-2-macroglobulin were validated via ELISA assay. These findings revealed significant changes in serum proteins in the AD mouse model at an early pathological stage and demonstrated that administration of CoQ10 could modulate these changes in serum proteins. Our study suggested that these differentially expressed serum proteins could serve as potential protein biomarkers of early AD and that screening for potential candidate AD therapeutic drugs and monitoring of therapeutic effects could be performed via measurement of the changes in these differentially expressed serum proteins.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Antioxidants; Blood Proteins; Databases, Protein; Disease Models, Animal; Electrophoresis, Gel, Two-Dimensional; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Humans; Mice; Mice, Transgenic; Mutation; Presenilin-1; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; tau Proteins; Ubiquinone

The aim of this study was to examine the role of coenzyme Q10 (CoQ10) in the prevention of steroid-induced osteonecrosis of the femoral head (ONFH) in rats.. The study included 20 Sprague-Dawley rats injected once with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle to induce osteonecrosis. Animals were divided into two equal groups; Group 1 received no prophylaxis (control group) and the Group 2 received CoQ10. Hematological examinations were performed before steroid injection (0 weeks) and at 4 weeks after steroid injection. Femoral heads were examined histologically to evaluate osteonecrosis.. Changes in blood glutathione (GSH) and malondialdehyde (MDA) concentrations were less significant in the CoQ10 group. The incidence of histologic changes consistent with early osteonecrosis was lower in the CoQ10 group (2 of 10; 20%) than the control group (7 of 10; 70%).. Coenzyme Q10 may be useful as a preventing agent in steroid-induced ONFH. Inhibited oxidative stress is a possible mechanism for this effect.

Topics: Animals; Disease Models, Animal; Femur Head; Glucocorticoids; Glutathione; Malondialdehyde; Methylprednisolone; Methylprednisolone Acetate; Osteonecrosis; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Treatment Outcome; Ubiquinone; Vitamins

HDL and apolipoprotein A1 (apoA1) concentrations inversely correlate with risk of death from ischemic heart disease; however, the role of apoA1 in the myocardial response to ischemia has not been well defined. To test whether apoA1, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarction via direct left anterior descending coronary artery ligation in apoA1 null (apoA1(-/-)) and apoA1 heterozygous (apoA1(+/-)) mice. We observed that apoA1(+/-) and apoA1(-/-) mice had a 52% and 125% increase in infarct size as a percentage of area at risk, respectively, compared with wild-type (WT) C57BL/6 mice. Mitochondrial oxidation contributes to tissue damage in ischemia-reperfusion injury. A substantial defect was present at baseline in the electron transport chain of cardiac myocytes from apoA1(-/-) mice localized to the coenzyme Q (CoQ) pool with impaired electron transfer (67% decrease) from complex II to complex III. Administration of coenzyme Q10 (CoQ10) to apoA1 null mice normalized the cardiac mitochondrial CoQ pool and reduced infarct size to that observed in WT mice. CoQ10 administration did not significantly alter infarct size in WT mice. These data identify CoQ pool content leading to impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA1. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL and low apoA1 concentrations that can be corrected by CoQ10 supplementation and suggest populations of patients that may benefit particularly from CoQ10 supplementation.

Topics: Animals; Antioxidants; Apolipoprotein A-I; Cardiotonic Agents; Dietary Supplements; Disease Models, Animal; Electron Transport; Electron Transport Complex II; Electron Transport Complex III; Heart; Hypoalphalipoproteinemias; Injections, Intraperitoneal; Intestinal Absorption; Male; Mice; Mice, Knockout; Mitochondria, Heart; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Tissue Distribution; Ubiquinone

Although the support for the use of antioxidants, such as coenzyme Q(10) (CoQ(10)), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ(10) is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ(10) (Ubisol-Q(10)) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q(10) was delivered in drinking water. Prophylactic application of Ubisol-Q(10), started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q(10) group by day 28). Therapeutic application of Ubisol-Q(10), given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q(10) concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ(10)/kg body weight/day, showing clearly that high doses of CoQ(10) were not required to deliver these effects. Furthermore, the Ubisol-Q(10) treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q(10) was capable of halting the neurodegeneration already in progress; however, to maintain it a continuous supplementation of Ubisol-Q(10) was required. The pathologic processes initiated by MPTP resumed if supplementation was withdrawn. We suggest that in addition to brain delivery of powerful antioxidants, Ubisol-Q(10) might have also supported subcellular oxidoreductase systems allowing them to maintain a favorable cellular redox status, especially in astroglia, facilitating their role in neuroprotection. Based on this data further clini

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Antioxidants; Astrocytes; Chemistry, Pharmaceutical; Disease Models, Animal; Dopaminergic Neurons; Male; Mice, Inbred C57BL; Micelles; Nanoparticles; Neuroprotective Agents; Oxidation-Reduction; Parkinson Disease; Ubiquinone

Coenzyme Q10 is a potent antioxidant in both mitochondria and lipid membranes. It has also been recognized to have an effect on gene expression. This study was designed to investigate whether acute or subchronic treatment with coenzyme Q10 altered the seizures induced by pentylenetetrazole or electroshock in mice. We also evaluated the involvement of nitric oxide in the effects of coenzyme Q10 in pentylenetetrazole-induced seizure models. Acute oral treatment with different doses of coenzyme Q10 did not affect the seizure in intraperitoneal pentylenetetrazole, intravenous pentylenetetrazole, and electroshock models in mice. Subchronic oral administration of coenzyme Q10 (100 mg/kg or more) increased time latencies to the onset of myoclonic jerks and clonic seizures induced by intraperitoneal pentylenetetrazole and at the doses of 25 mg/kg or more increased the seizure threshold induced by intravenous infusion of pentylenetetrazole. Subchronic doses of coenzyme Q10 (50 mg/kg or more) also decreased the incidence of tonic seizures in the electroshock-induced seizure model. Moreover, acute treatment with the precursor of nitric oxide synthesis, L-arginine (60 mg/kg), led to a significant potentiation of the antiseizure effects of subchronic administration of coenzyme Q10 (400 mg/kg in intraperitoneal and 6.25 mg/kg in intravenous pentylenetetrazole tests). Acute treatment with l-NAME (5 mg/kg), a nonspecific nitric oxide synthase inhibitor, significantly attenuated the antiseizure effects of subchronic doses of coenzyme Q10 in both seizure models induced by pentylenetetrazole. On the other hand, acute administration of aminoguanidine (100 mg/kg), a specific inducible nitric oxide synthase inhibitor, did not affect the seizures in mice treated with subchronic doses of coenzyme Q10 in both intraperitoneal and intravenous pentylenetetrazole tests. In conclusion, only subchronic and not acute administration of coenzyme Q10 attenuated seizures induced by pentylenetetrazole or electroshock. We also demonstrated, for the first time, the interaction between nitric oxide and coenzyme Q10 in antiseizure activity probably through the induction of constitutive nitric oxide synthase.

Topics: Animals; Arginine; Brain; Disease Models, Animal; Electroshock; Epilepsy, Tonic-Clonic; Guanidines; Male; Mice; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Pentylenetetrazole; Seizures; Ubiquinone

Parkinson's disease arises from a combination of environmental and genetic risk factors. At present neither the curative nor preventative therapies are available; hence, there is an urgent need to develop reliable animal models to facilitate their development. Water soluble nanomiceller formulation of CoQ10 (Ubisol-Q10) has shown neuroprotection against neurotoxin on human neuronal cells. We have combined the genetic deficiency of DJ-1/PARK7 mice with MPTP exposure and develop a genetic susceptibility model of PD and evaluated the neuroprotective efficacy of (Ubisol-Q10).. Transgenic mice with DJ-1 deficiency (DJ-1/PARK7) were given either water or Ubisol-Q10 prophylactically at a dose of 6 mg/kg/day added directly to a drinking water for one month followed challenged with MPTP injections while keeping the same drinking water regiments. Four weeks after the last injection we evaluated neuroprotective efficacy of Ubisol-Q10 in DJ-1/MPTP model of PD using histochemical and behavioral readouts.. We confirmed genetic susceptibility to MPTP and showed that prophylactic oral treatment with Ubisol-Q10 significantly offset the neurotoxicity and ameliorated motor dysfunction, otherwise correlated with the MPTP injury.. Ubisol-Q10 protects against MPTP-induced neurodegeneration and motor dysfunction in DJ-1 deficient mice. Ubisol-Q10 might be a treatment prospect for people genetically predisposed to PD as well as with sporadic PD.

Topics: Animals; Disease Models, Animal; Genetic Predisposition to Disease; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; MPTP Poisoning; Neurons; Neuroprotective Agents; Oncogene Proteins; Pars Compacta; Peroxiredoxins; Protein Deglycase DJ-1; Tyrosine 3-Monooxygenase; Ubiquinone

The influence of coenzyme Q10 (CoQ10) on early ischemic deterioration was studied on Wistar rats with experimental myocardial infarction. CoQ10 (30 mg/kg) was injected intravenously 10 min after coronary artery occlusion, and morphometric analysis was performed for 72 h after the onset of ischemia. CoQ10-treated rats had restricted total myocardial damage (by 52%), including areas of necrosis (by 84%) and areas of cellular inflammatory infiltration (by 38%) as compared to saline-treated rats (p < 0.001).

Topics: Animals; Disease Models, Animal; Male; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Ubiquinone; Vitamins

Multiple sclerosis (MS) is known as a progressive central nervous system inflammatory disease. Certain factors, such as interleukins, inflammatory cells, and oxidative stress are supposed to involve in MS etiology. Because of the important role of oxidative stress, antioxidant therapy for MS has received more attention. Although coenzyme Q10 (CoQ10) acts as an antioxidant, there is a lack of enough research on its effects on MS. Therefore, the present research was designed.. C57BL/6 female adult mice (n = 30) were used in this study. The animals were randomly divided into trial and control groups. To induce MS, routine procedure for experimental autoimmune encephalomyelitis (EAE) was used, and scoring was performed based on clinical signs. By detecting score one, CoQ10 administration was started (10 mg/kg/three weeks). By using ELISA and real-time PCR, the brain levels of TNF-, IL-10, IL-4, and IL-12 were studied. Statistical tests were used to analyze the data and the P value less than 0.05 was considered to be significant.. Clinical symptoms in EAE animals were significantly decreased (P<0.05) as compared to control ones. In addition, the level of the TNF- was significantly decreased following CoQ10 administration versus IL-10. The ratio of TH1/TH2 interleukins in treated animals was significantly less than that in non-treated animals (P<0.01).. Our findings showed that CoQ10 is capable of suppressing the inflammatory pathway of MS.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Gene Expression; Interleukin-10; Interleukin-12; Interleukin-4; Mice; Mice, Inbred C57BL; Multiple Sclerosis; RNA, Messenger; Th1 Cells; Th2 Cells; Tumor Necrosis Factor-alpha; Ubiquinone

Myocardial ischemia (MI) remains one of the leading causes of death worldwide. Angiogenic therapy with the vascular endothelial growth factor (VEGF) is a promising strategy to overcome hypoxia and its consequences. However, from the clinical data it is clear that fulfillment of the potential of VEGF warrants a better delivery strategy. On the other hand, the compelling evidences of the role of oxidative stress in diseases like MI encourage the use of antioxidant agents. Coenzyme Q10 (CoQ10) due to its role in the electron transport chain in the mitochondria seems to be a good candidate to manage MI but is associated with poor biopharmaceutical properties seeking better delivery approaches. The female Sprague Dawley rats were induced MI and were followed up with VEGF microparticles intramyocardially and CoQ10 nanoparticles orally or their combination with appropriate controls. Cardiac function was assessed by measuring ejection fraction before and after three months of therapy. Results demonstrate significant improvement in the ejection fraction after three months with both treatment forms individually; however the combination therapy failed to offer any synergism. In conclusion, VEGF microparticles and CoQ10 nanoparticles can be considered as promising strategies for managing MI.

Topics: Animals; Cell Proliferation; Coronary Vessels; Disease Models, Animal; Female; Human Umbilical Vein Endothelial Cells; Humans; Lactic Acid; Myocardial Ischemia; Myocardium; Nanoparticles; Neovascularization, Physiologic; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Stroke Volume; Ubiquinone; Vascular Endothelial Growth Factor A

The early onset of type 2 diabetes mellitus (DM), driven by increasing obesity, is associated with peripheral neuropathy. Here, we characterize diabetic neuropathic pain in New Zealand obese diabetic mice (NZO/HILtJ) as a polygenic model of obesity with type 2 diabetes and investigate the role of coenzyme Q10 (CoQ10) in the prevention and treatment of diabetic neuropathic pain. Since the overexpression of mitogen-activated protein kinase (MAPK), nuclear factor-κB proteins (NF-Kb), toll-like receptor 4 (TLR4) and downstream cytokines (such as CCL2, CXCL10) are considered important factors contributing to the development of neuropathic pain, the expression of these factors and the inhibitory effects of CoQ10 were evaluated. NZO/HILtJ mice spontaneously developed type 2 DM and increased body mass with diabetic neuropathic pain. CoQ10 treatment decreased pain hypersensitivity and long-term supplementation prevented the development of diabetic neuropathic pain but did not attenuate diabetes. Spinal cord, blood serum, liver tissue, and dorsal root ganglia (DRG) from diabetic mice demonstrated increased lipid peroxidation, which was decreased by CoQ10 treatment. The percentage of positive neurons of p65 (the activated marker of NF-KB) and MAPK in DRG were significantly higher in DM mice compared to controls. However, CoQ10 treatment significantly decreased p65 and MAPK positive neurons in the DRG of DM mice. RT-PCR demonstrated that elevated levels of mRNA of CCL2, CXCL10 or TLR4 in the spinal cord of DM mice decreased significantly when DM mice were treated with CoQ10.. This model may be useful in understanding the mechanisms of neuropathic pain in type 2 DM induced neuropathic pain and may facilitate preclinical testing of therapies. CoQ10 may decrease oxidative stress in the central and peripheral nervous system by acting as an anti-oxidant and free-radical scavenger. These results suggest that CoQ10 might be a reasonable preventative strategy for long-term use and using CoQ10 treatment may be a safe and effective long-term approach in the treatment of diabetic neuropathy.

Topics: Age Factors; Animals; Blood Glucose; Body Weight; Chemokine CCL2; Chemokine CXCL10; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Models, Animal; Female; Gene Expression Regulation; Hyperalgesia; Lipid Peroxidation; Male; Mice; Pain Measurement; Pain Threshold; Recombinant Fusion Proteins; Toll-Like Receptor 4; Ubiquinone; Vitamins

To investigate the effects of coenzyme Q10 pretreatment on the expressions of Bcl-2, Bax and glycogen synthase kinase-3β (GSK-3β) in rats suffering from ischemia/reperfusion injury.. Thirty-six adult male SD rats were randomly assigned into 3 groups: sham-operated group (sham), ischemia/reperfusion group (I/R) and coenzyme Q10 preconditioning group (Q10). Focal cerebral ischemia/reperfusion models were established in experimental rats by blocking middle cerebral artery with suture. Histological changes of hippocampal neurons were observed by HE staining. The expressions of Bcl-2, Bax and GSK-3β were detected by immunohistochemistry and Western blotting.. Immunohistochemistry showed that the percentage of Bcl-2 positive cells increased in the hippocampus, while the percentages of Bax and GSK-3β positive cells decreased in Q10 group compared with I/R group. Western blotting revealed that the expression level of Bcl-2 was higher and the expression levels of Bax and GSK-3β were lower in Q10 group than in I/R group. There were significant differences between the two groups (P<0.05).. Coenzyme Q10 promoted the expression of Bcl-2 and suppressed the expressions of Bax and GSK-3β in the hippocampus of rats exposed to cerebral ischemia/reperfusion.

Topics: Animals; bcl-2-Associated X Protein; Brain Ischemia; CA1 Region, Hippocampal; Disease Models, Animal; Gene Expression Regulation; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Male; Proto-Oncogene Proteins c-bcl-2; Rats; Reperfusion Injury; Ubiquinone

To investigate the effect of CoenzymeQ10 (CoQ10) on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA).. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration of CoQ10 was initiated on day 4 after MIA injection. Pain severity was assessed by measuring secondary tactile allodynia using the von Frey assessment test. The degree of cartilage degradation was determined by measuring cartilage thickness and the amount of proteoglycan. The mankin scoring system was also used. Expressions of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), IL-6, IL-15, inducible nitric oxide synthase (iNOS), nitrotyrosine and receptor for advanced glycation end products (RAGE) were analyzed using immunohistochemistry.. Treatment with CoQ10 demonstrated an antinociceptive effect in the OA animal model. The reduction in secondary tactile allodynia was shown by an increased pain withdrawal latency and pain withdrawal threshold. CoQ10 also attenuated cartilage degeneration in the osteoarthritic joints. MMP-13, IL-1β, IL-6, IL-15, iNOS, nitrotyrosine and RAGE expressions were upregulated in OA joints and significantly reduced with CoQ10 treatment.. CoQ10 exerts a therapeutic effect on OA via pain suppression and cartilage degeneration by inhibiting inflammatory mediators, which play a vital role in OA pathogenesis.

Topics: Analgesics; Animals; Cartilage; Cytokines; Disease Models, Animal; Gene Expression Regulation; Inflammation; Iodoacetic Acid; Male; Matrix Metalloproteinase 13; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis; Pain; Rats; Rats, Wistar; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Ubiquinone

Several recent studies suggest a close link between mitochondrial dysfunction and depression. Coenzyme Q10 (CoQ10) is a mobile electron carrier in the mitochondrial respiratory chain (MRC) with antioxidant and potential neuroprotective activities. This study investigated the effect of chronic administration of CoQ10 (50, 100, and 200 mg/kg/day, intraperitoneally, for 4 weeks) on anhedonia and on the activities of MRC complexes and creatine kinase in the frontal cortex and hippocampus of Wistar rats subjected to chronic restraint stress (CRS, 6 h × 28 days). Exposure to CRS-induced anhedonic-like behavior (decreased sucrose preference), reduced body weight gain and food intake, increased adrenal gland weight, and altered the activity of the MRC complexes in the brain areas tested. CoQ10 dose-dependently antagonized CRS-induced depressive behavior by increasing sucrose preference (reversal of anhedonia), body weight, and food intake and reducing adrenal gland weight. CoQ10 also enhanced the activities of MRC complexes (I-IV) and creatine kinase in the frontal cortex and hippocampus. Thus, the reversal of CRS-induced anhedonia may be partially mediated by amelioration of brain mitochondrial function. The findings also support the hypothesis that brain energy impairment is involved in the pathophysiology of depression and enhancing mitochondrial function could provide an opportunity for development of a potentially more efficient drug therapy for depression.

Topics: Anhedonia; Animals; Antioxidants; Brain; Creatine Kinase; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Electron Transport; Male; Mitochondria; Rats; Rats, Wistar; Restraint, Physical; Stress, Psychological; Sucrose; Ubiquinone

Identification of single-gene causes of steroid-resistant nephrotic syndrome (SRNS) has furthered the understanding of the pathogenesis of this disease. Here, using a combination of homozygosity mapping and whole human exome resequencing, we identified mutations in the aarF domain containing kinase 4 (ADCK4) gene in 15 individuals with SRNS from 8 unrelated families. ADCK4 was highly similar to ADCK3, which has been shown to participate in coenzyme Q10 (CoQ10) biosynthesis. Mutations in ADCK4 resulted in reduced CoQ10 levels and reduced mitochondrial respiratory enzyme activity in cells isolated from individuals with SRNS and transformed lymphoblasts. Knockdown of adck4 in zebrafish and Drosophila recapitulated nephrotic syndrome-associated phenotypes. Furthermore, ADCK4 was expressed in glomerular podocytes and partially localized to podocyte mitochondria and foot processes in rat kidneys and cultured human podocytes. In human podocytes, ADCK4 interacted with members of the CoQ10 biosynthesis pathway, including COQ6, which has been linked with SRNS and COQ7. Knockdown of ADCK4 in podocytes resulted in decreased migration, which was reversed by CoQ10 addition. Interestingly, a patient with SRNS with a homozygous ADCK4 frameshift mutation had partial remission following CoQ10 treatment. These data indicate that individuals with SRNS with mutations in ADCK4 or other genes that participate in CoQ10 biosynthesis may be treatable with CoQ10.

Topics: Adolescent; Adrenal Cortex Hormones; Amino Acid Sequence; Animals; Cells, Cultured; Child; Consanguinity; Conserved Sequence; Disease Models, Animal; DNA Mutational Analysis; Drosophila Proteins; Drug Resistance; Exome; Fibroblasts; Gene Knockdown Techniques; Humans; Mitochondria; Molecular Sequence Data; Mutation; Nephrotic Syndrome; Podocytes; Protein Kinases; Rats; Sequence Alignment; Sequence Homology, Amino Acid; Ubiquinone; Young Adult; Zebrafish; Zebrafish Proteins

Cisplatin or cis-diamminedichloroplatinum (II) (CDDP) is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG) with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA), and coenzyme Q10 (CoQ10), in cisplatin (2 mg/kg i.p. twice weekly) induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po) with resveratrol (10 mg/kg/day i.p.) or ALA (20 mg/kg/day i.p.) or CoQ10 (10 mg/kg weekly thrice i.p.) exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.

Topics: Animals; Behavior, Animal; Catalase; Disease Models, Animal; Drug Therapy, Combination; Glutathione; Lipid Peroxidation; Neural Conduction; Neuroprotective Agents; Peripheral Nervous System Diseases; Psychomotor Performance; Rats; Resveratrol; Sciatic Neuropathy; Sodium Glutamate; Stilbenes; Thioctic Acid; Ubiquinone

Fibromyalgia (FM) is a complex disorder that affects up to 5% of the general population worldwide. Both mitochondrial dysfunction and inflammation have been implicated in the pathophysiology of FM. We have investigated the possible relationship between mitochondrial dysfunction, oxidative stress, and inflammation in FM. We studied 30 women diagnosed with FM and 20 healthy women. Blood mononuclear cells (BMCs) from FM patients showed reduced level of coenzyme Q₁₀ (CoQ₁₀) and mtDNA contents and high level of mitochondrial reactive oxygen species (ROS) and serum tumor necrosis factor (TNF)-alpha and transcript levels. A significant negative correlation between CoQ₁₀ and TNF-alpha levels (r=-0.588; p<0.01), and a positive correlation between ROS and TNF-alpha levels (r=0.791; p<0.001) were observed accompanied by a significant correlation of visual analogical scale with serum TNF-alpha and transcript levels (r=0.4507; p<0.05 and r=0.7089; p<0.001, respectively). TNF-alpha release was observed in an in vitro (BMCs) and in vivo (mice) CoQ₁₀ deficiency model. Oral CoQ₁₀ supplementation restored biochemical parameters and induced a significant improvement in clinical symptoms (p<0.001). These results lead to the hypothesis that inflammation could be a mitochondrial dysfunction-dependent event implicated in the pathophysiology of FM in several patients indicating at mitochondria as a possible new therapeutic target.

Topics: Animals; Disease Models, Animal; Female; Fibromyalgia; Humans; Inflammation; Leukocytes, Mononuclear; Male; Mice; Mitochondria; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Ubiquinone

Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and the most resistant type to treatment. Novel treatment approaches are strongly required to prevent or even reverse the cellular and molecular mechanisms of epileptogenesis. In this study, we investigated the possible neuroprotective effect of coenzyme Q10 (CoQ10) in an intrahippocampal kainate model of TLE in rat. Kainate injection caused a higher seizure severity during status epilepticus and spontaneous seizure phases, and CoQ10 pretreatment significantly attenuated its severity and incidence rate. Intrahippocampal kainate also led to elevation of malondialdehyde (MDA) and nitrite, and CoQ10 significantly attenuated the increased MDA and nitrite content. In addition, intrahippocampal kainate induced a significant degeneration of neurons in CA1, CA3, and hilar regions of the hippocampus, and CoQ10 significantly attenuated these changes in CA1 and CA3 regions. Timm's staining data showed a robust mossy fiber sprouting (MFS) in dentate gyrus of kainate-lesioned rats and CoQ10 significantly lowered MFS intensity. These data suggest that CoQ10 pretreatment could attenuate spontaneous recurrent seizures and inhibit hippocampal neuronal loss and aberrant MFS in kainate-induced model of TLE in rat, and part of its beneficial effect is due to its potential to mitigate oxidative stress.

Topics: Animals; Cell Death; Disease Models, Animal; Epilepsy, Temporal Lobe; Kainic Acid; Malondialdehyde; Mossy Fibers, Hippocampal; Neuroprotective Agents; Nitrites; Oxidative Stress; Rats; Status Epilepticus; Ubiquinone; Vitamins

The aim of the present investigation was to evaluate the effect of Coenzyme Q10 and its combination with vitamin E in alcohol-induced chronic neuropathic pain. Male Wistar rats were orally treated with alcohol (10 g/kg, 35% v/v, b.i.d.) for 10 weeks. Coenzyme Q10 (25, 50, and 100 mg/kg) and vitamin E (100 mg/kg) were coadministered orally for 1 h after ethanol administration for 10 weeks. Various nerve functions, biochemical, and molecular parameters were assessed. Chronic administration of ethanol for 10 weeks resulted significant development of neuropathic pain. Treatment with Coenzyme Q10 (50 and 100 mg/kg) for 10 weeks showed significant and dose dependently increased in level of nociceptive threshold, endogenous antioxidant, and Na,K-ATPase enzyme. Coenzyme Q10 (50 and 100 mg/kg) significantly restored the levels of motor nerve conduction velocity and sensory nerve conduction velocity. It also showed significant decrease in levels of endogenous calcium, oxidative-nitrosative stress, TNF-α, IL-1β, and IL-4 level. Alteration in protein expression of polymerase gamma (pol γ) was significantly restored the Coenzyme Q10 treatment. The important finding of the study is that, Coenzyme Q10 (100 mg/kg) and α-tocopherol (100 mg/kg) combination-treated rats showed more significant prevention of behavioral, biochemical, and molecular neurotoxic effect of alcohol administration than Coenzyme Q10 or α-tocopherol alone treated group. It is evident from the finding of present investigation that plethora of mechanism including inhibition of oxido-nitrosative stress, release of pro-inflammatory cytokine, modulation of endogenous biomarker, and protection of pol γ protein expression simultaneously orchestrate to exhibits neuroprotective effect of Coenzyme Q10, vitamin E and their combination.

Topics: Administration, Oral; Alcoholic Neuropathy; Animals; Calcium; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanol; Interleukin-1beta; Interleukin-4; Male; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Ubiquinone; Vitamin E

Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the high-CoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after age-related declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, high-CoQ intake may be beneficial.

Topics: Aging; Animals; Behavior, Animal; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Learning; Locomotion; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Oxidation-Reduction; Proteins; Ubiquinone; Vitamins

We investigated the protective effects of coenzyme Q10 on bladder dysfunction in a rat model of atherosclerosis induced chronic bladder ischemia.. A total of 24 male Sprague-Dawley® rats at age 16 weeks were divided into 4 groups of 6 each, including group 1--untreated, sham operated rats, group 2--coenzyme Q10 treated, sham operated rats, group 3--untreated rats with chronic bladder ischemia and group 4--coenzyme Q10 treated rats with chronic bladder ischemia. Groups 3 and 4 received an endothelial injury to the iliac arteries and were fed a 2% cholesterol diet for 8 weeks. Groups 2 and 4 were treated with coenzyme Q10 and the others were treated with vehicle for 4 weeks. Eight weeks postoperatively we performed continuous in vivo cystometry, an in vitro detrusor muscle strip study and a malondialdehyde assay. Histological examination of the bladder walls and iliac arteries was also done.. In vivo cystometry revealed that coenzyme Q10 administration after the induction of chronic bladder ischemia prolonged micturition frequency and the intercontraction interval, and increased bladder capacity compared to those in untreated rats with chronic bladder ischemia. In the detrusor muscle strip study coenzyme Q10 administration after the induction of chronic bladder ischemia increased contractile responses compared to those in untreated rats with chronic bladder ischemia. Rats with chronic bladder ischemia also showed higher malondialdehyde in bladder tissue and serum than the other groups. Chronic bladder ischemia induced submucosal fibrosis of the bladder walls and a degenerative change in the blood vessel tunical media, as shown on histological examination.. Our study suggests that coenzyme Q10 acts as an antioxidant to protect bladder function in this chronic bladder ischemia model.

Topics: Animals; Biopsy, Needle; Chronic Disease; Disease Models, Animal; Immunohistochemistry; Ischemia; Male; Malondialdehyde; Muscle Contraction; Oxidative Stress; Protective Agents; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Sensitivity and Specificity; Ubiquinone; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics

Multiple evidences suggest that depression is accompanied by an induction of oxidative/nitrosative stress (O&NS) pathways and by a reduced antioxidant status. Coenzyme Q10 (CoQ10) is an essential cofactor in the mitochondrial electron transport pathway and has a powerful antioxidant capacity.. This study investigated the effect of chronic treatment with CoQ10 (25, 50, 100 and 150 mg/kg/day, i.p. for 3 weeks) on depressive-like behavior and hippocampal, O&NS, and DNA damage, induced by chronic restraint stress (CRS), an experimental model of depression, in rats.. CoQ10 showed a significant antidepressant effect, as evidenced by amelioration of CRS-induced behavioral aberrations in forced swimming and open field tests, elevated corticosterone level and body weight loss. Moreover, CoQ10 dose-dependently restored the hippocampal catalase, glutathione peroxidase and reduced glutathione and decreased the hippocampal malondialdehyde, nitric oxide and 8-hydroxy-2'-deoxyguanosine levels, which indicated a potential protective effect of CoQ10 against hippocampal O&NS lipid peroxidation and DNA damage.. CoQ10 possesses antidepressant activity and can protect against CRS-induced hippocampal DNA damage which could be mediated in part by maintaining mitochondrial function and its well documented antioxidant properties. Therefore, CoQ10 may have a potential therapeutic value for the management of depressive disorders. However, further research, is still required to characterize the mechanism of the antidepressant effect of CoQ10 and extend these results before the safe application in humans.

Topics: Animals; Antidepressive Agents; Antioxidants; Behavior, Animal; Corticosterone; Depression; Disease Models, Animal; DNA Damage; Hippocampus; Male; Oxidative Stress; Rats; Rats, Wistar; Reactive Nitrogen Species; Restraint, Physical; Stress, Physiological; Ubiquinone

Oxidative stress is a key factor implicated in the development of diabetic neuropathy. This study evaluates the prophylactic and antinociceptive effects of the antioxidant coenzyme Q10 (CoQ10) on diabetes-induced neuropathic pain in a diabetic mouse model.. Total 56 mice with type 1 diabetes induced by streptozotocin were used, 20 normal mice were used as control. Mechanical and thermal nociceptive behavioral assays were applied to evaluate diabetic neuropathic pain. Tissue lipid peroxidation, immunohistochemistry, reverse transcription, and polymerase chain reaction were used to evaluate the molecular mechanisms of CoQ10. Data are presented as mean ± SEM.. CoQ10 administration was associated with reduced loss of body weight compared with nontreated diabetic mice, without affecting blood glucose levels. Low dose and long-term administration of CoQ10 prevented the development of neuropathic pain. Treatment with CoQ10 produced a significant dose-dependent inhibition of mechanical allodynia and thermal hyperalgesia in diabetic mice. Dorsal root ganglia, sciatic nerve, and spinal cord tissues from diabetic mice demonstrated increased lipid peroxidation that was reduced by CoQ10 treatment. CoQ10 administration was also noted to reduce the proinflammatory factors in the peripheral and central nervous system.. The results of this study support the hypothesis that hyperglycemia induced neuronal oxidative damage and reactive inflammation may be pathogenic in diabetic neuropathic pain. CoQ10 may be protective by inhibiting oxidative stress and reducing inflammation by down-regulating proinflammatory factors. These results suggest that CoQ10 administration may represent a low-risk, high-reward strategy for preventing or treating diabetic neuropathy.

Topics: Analgesics; Animals; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Disease Models, Animal; Dose-Response Relationship, Drug; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; Ubiquinone; Vitamins; Weight Loss

Controversies surround the usefulness of Coenzyme Q10 (CoQ10) in Huntington's disease (HD), an autosomal dominant, fatal, neurodegenerative disease with no cure or disease modifying treatment. CoQ10, an endogenous substrate for electron transport and an anti-oxidant, has been shown in some but not all studies to improve symptoms and survival in mouse models of HD. Previous studies have been conducted in fast-progressing models that better mimic the juvenile forms of HD than the much more common middle-age onset form, possibly accounting for mixed results. Establishing the usefulness of CoQ10 to alter HD disease course in a model that better recapitulates the progressive features of the human disorder is important because clinical trials of CoQ10, which is safe and well tolerated, are being planned in patients. The CAG140 knock-in (KI) mouse model of HD in which an expanded (approximately 120) CAG repeat is inserted in the mouse gene provides a model of the mutation in the proper genomic and protein context. These mice display progressive motor, cognitive and emotional anomalies, transcriptional disturbances and late striatal degeneration. Homozygote mutant CAG140 KI mice and wild-type littermates were fed CoQ10 (0.2%, 0.6%) in chow, and behavioral and pathological markers of disease were examined. CoQ10 improved early behavioral deficits and normalized some transcriptional deficits without altering huntingtin aggregates in striatum. The lower dose (0.2%) was more beneficial than 0.6%. Similar to previous studies, this low dose also induced deleterious effects in open field and rotarod in WT mice, however these effects are of unclear clinical significance in view of the excellent safety profile of CoQ10 in humans. These data confirm that CoQ10 may be beneficial in HD but suggest that maximum benefit may be observed when treatment is begun at early stages of the disease and that dosage may be critical.

Topics: Animals; Behavior, Animal; Dietary Supplements; Disease Models, Animal; Female; Humans; Huntington Disease; Male; Mice; Mice, Transgenic; Motor Activity; Ubiquinone

The present study was carried out to elucidate the effects of coenzyme Q(10) (CoQ(10)) against cognitive impairments induced by dichlorvos (DDVP). We have previously shown organophosphate, DDVP-induced impairments in neurobehavioral indices viz. rota rod, passive avoidance, and water maze tests. In addition to this, we have also reported that chronic DDVP exposure leads to decreased mitochondrial electron transfer activities of cytochrome oxidase along with altered mitochondrial complexes I-III activity. Administration of CoQ(10) (4.5 mg/kg, i.p. for 12 weeks prior to DDVP administration daily) to DDVP-treated rats improved cognitive performance in passive avoidance task and Morris water maze test. Furthermore, CoQ(10) treatment also reduced oxidative stress (as evident by reduced malondialdehyde, decreased ROS and increased Mn-SOD activity) in DDVP-treated rats' hippocampus region, along with enhanced activity of complexes I-III and complex IV. Electron microscope studies of rat hippocampus mitochondria revealed that CoQ(10) administration leads to near normal physiology of mitochondria with well-defined cristae compared with DDVP-treated animals where enlarged mitochondria with distorted cristae are observed. CoQ(10) administration also attenuated neuronal damage in hippocampus as evident from histopathological studies. These results demonstrate the beneficial effects of CoQ(10) against organophosphate-induced cognitive impairments and hippocampal neuronal degeneration.

Topics: Animals; Avoidance Learning; Cognition Disorders; Dichlorvos; Disease Models, Animal; Drug Administration Schedule; Hippocampus; Male; Maze Learning; Mitochondria; Nerve Degeneration; Oxidative Stress; Proton Pumps; Rats; Rats, Wistar; Ubiquinone; Vitamins

The potential protective effect of coenzyme Q10 against acute liver injury induced by a single dose of acetaminophen (700 mg/kg, p.o.) was investigated in rats. Coenzyme Q10 treatment was given as two i.p. injections, 10 mg/kg each, at 1 and 12 h following acetaminophen administration. Coenzyme Q10 significantly reduced the levels of serum aminotransferases, suppressed lipid peroxidation, prevented the decreases of reduced glutathione and catalase activity, decreased the elevations of tumor necrosis factor-α and nitric oxide as well as attenuating the reductions of selenium and zinc ions in liver tissue resulting from acetaminophen administration. Histopathological liver tissue damage mediated by acetaminophen was ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the acetaminophen-induced overexpression of inducible nitric oxide synthase, nuclear factor-κB, caspase-3 and p53 in liver tissue. It was concluded that coenzyme Q10 protects rat liver against acute acetaminophen hepatotoxicity, most probably through its antioxidant, anti-inflammatory and antiapoptotic effects.

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Biomarkers; Caspase 3; Catalase; Chemical and Drug Induced Liver Injury; Cytoprotection; Disease Models, Animal; Drug Administration Schedule; Glutathione; Immunohistochemistry; Injections, Intraperitoneal; Lipid Peroxidation; Liver; Male; Malondialdehyde; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidative Stress; Rats; Rats, Sprague-Dawley; Selenium; Time Factors; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53; Ubiquinone; Zinc

Increased oxygen consumption results in kidney tissue hypoxia, which is proposed to contribute to the development of diabetic nephropathy. Oxidative stress causes increased oxygen consumption in type 1 diabetic kidneys, partly mediated by uncoupling protein-2 (UCP-2)-induced mitochondrial uncoupling. The present study investigates the role of UCP-2 and oxidative stress in mitochondrial oxygen consumption and kidney function in db/db mice as a model of type 2 diabetes.. Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment.. Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7 ± 0.1 vs 0.2 ± 0.1 pmol O(2) s(-1) [mg protein](-1)), glomerular hyperfiltration (502 ± 26 vs 385 ± 3 μl/min), increased proteinuria (21 ± 2 vs 14 ± 1, μg/24 h), mitochondrial fragmentation (fragmentation score 2.4 ± 0.3 vs 0.7 ± 0.1) and size (1.6 ± 0.1 vs 1 ± 0.0 μm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (-1.1 ± 0.1 pmol O(2) s(-1) [mg protein](-1)). UCP-2 protein levels were similar in untreated control and db/db mice (67 ± 9 vs 67 ± 4 optical density; OD) but were reduced in CoQ10 treated groups (43 ± 2 and 38 ± 7 OD).. db/db mice displayed oxidative stress-mediated activation of UCP-2, which resulted in mitochondrial uncoupling and increased oxygen consumption. CoQ10 prevented altered mitochondrial function and morphology, glomerular hyperfiltration and proteinuria in db/db mice, highlighting the role of mitochondria in the pathogenesis of diabetic nephropathy and the benefits of preventing increased oxidative stress.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Glomerular Filtration Rate; Guanosine Diphosphate; Ion Channels; Kidney Glomerulus; Mice; Mitochondria; Mitochondrial Proteins; Oxidative Stress; Oxygen Consumption; Proteinuria; Ubiquinone; Uncoupling Protein 2; Vitamins

An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q(10) would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q(10) to that of the ACE inhibitor ramipril.. Six-week-old non-diabetic db/+ mice and diabetic db/db mice received either normal drinking water or water supplemented with coenzyme Q(10) for 10 weeks. Endpoint cardiac function was assessed by echocardiography and catheterisation. Ventricular tissue was collected for histology, gene expression and protein analysis.. Untreated db/db diabetic mice exhibited hyperglycaemia, accompanied by diastolic dysfunction and adverse structural remodelling, including cardiomyocyte hypertrophy, myocardial fibrosis and increased apoptosis. Systemic lipid peroxidation and myocardial superoxide generation were also elevated in db/db mice. Coenzyme Q(10) and ramipril treatment reduced superoxide generation, ameliorated diastolic dysfunction and reduced cardiomyocyte hypertrophy and fibrosis in db/db mice. Phosphorylation of Akt, although depressed in untreated db/db mice, was restored with coenzyme Q(10) administration. We postulate that preservation of cardioprotective Akt signalling may be a mechanism by which coenzyme Q(10)-treated db/db mice are protected from pathological cardiac hypertrophy.. These data demonstrate that coenzyme Q(10) attenuates oxidative stress and left ventricular diastolic dysfunction and remodelling in the diabetic heart. Addition of coenzyme Q(10) to the current therapy used in diabetic patients with diastolic dysfunction warrants further investigation.

Topics: Animals; Antihypertensive Agents; Apoptosis; Cardiomegaly; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Disease Models, Animal; Endomyocardial Fibrosis; Female; Hyperglycemia; Lipid Peroxidation; Mice; Mice, Inbred C57BL; Oxidative Stress; Proto-Oncogene Proteins c-akt; Ramipril; Superoxides; Ubiquinone; Ultrasonography; Ventricular Remodeling; Vitamins

The goal of our study is to evaluate the effects of antioxidant vitamins (vitamin C and E), Coenzyme Q10 (CoQ10) and dexamethasone (Dxm) in experimental rat models with pulmonary contusion (PC).. Rats were randomly divided into six groups. Except for the control, all subgroups had a moderate pulmonary contusion. Animals in the group I and group II received intraperitoneal saline, group III received 10mg.kg-1 CoQ10 group IV received 100mg.kg-1 vitamin C, group V received 150 mg.kg-1 vitamin E, and group VI received 10mg.kg-1 Dxm. Blood gas analysis, serum nitric oxide (NO) and malondialdehyde (MDA) levels as well as superoxide dismutase (SOD) activity assays, bronchoalveolar lavage (BAL) fluid and histopathological examination were performed.. Administration of CoQ10 resulted in a significant increase in PaO2 values compared with the group I (p = 0.004). Levels of plasma MDA in group II were significantly higher than those in the group I (p = 0.01). Early administration of vitamin C, CoQ10, and Dxm significantly decreased the levels of MDA (p = 0.01). Lung contusion due to blunt trauma significantly decreased SOD activities in rat lung tissue compared with group I (p = 0.01). SOD levels were significantly elevated in animals treated with CoQ10, Vitamin E, or Dxm compared with group II (p = 0.01).. In our study, CoQ10, vitamin C, vitamin E and Dxm had a protective effect on the biochemical and histopathological outcome of PC after experimental blunt thorax trauma.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Dexamethasone; Disease Models, Animal; Histocytochemistry; Lung Injury; Male; Neutrophils; Rats; Rats, Wistar; Statistics, Nonparametric; Ubiquinone; Vitamin E; Vitamins

To evaluate if coenzyme Q10 (CoQ10) can protect retinal ganglion cells (RGCs) from apoptosis and, when instilled as eye drops on the cornea, if it can reach the retina and exert its antiapoptotic activity in this area in a mouse model of kainate (KA)-induced retinal damage.. Rat primary or cultured RGCs were subjected to glutamate (50 μM) or chemical hypoxia (Antimycin A, 200 μM) or serum withdrawal (FBS, 0.5%) in the presence or absence of CoQ10 (10 μM). Cell viability was evaluated by light microscopy and fluorescence-activated cell sorting analyses. Apoptosis was evaluated by caspase 3/7 activity and mitochondrion depolarization tetramethylrhodamine ethyl ester analysis. CoQ10 transfer to the retina following its instillation as eye drops on the cornea was quantified by HPLC. Retinal protection by CoQ10 (10 μM) eye drops instilled on the cornea was then evaluated in a mouse model of KA-induced excitotoxic retinal cell apoptosis by cleaved caspase 3 immunohistofluorescence, caspase 3/7 activity assays, and quantification of inhibition of RGC loss.. CoQ10 significantly increased viable cells by preventing RGC apoptosis. Furthermore, when topically applied as eye drops to the cornea, it reached the retina, thus substantially increasing local CoQ10 concentration and protecting retinal layers from apoptosis.. The ability of CoQ10 eye drops to protect retinal cells from apoptosis in the mouse model of KA-induced retinal damage suggests that topical CoQ10 may be evaluated in designing therapies for treating apoptosis-driven retinopathies.

Topics: Administration, Topical; Animals; Antimycin A; Apoptosis; Caspase 3; Caspase 7; Cell Count; Cell Survival; Cells, Cultured; Chromatography, High Pressure Liquid; Cornea; Disease Models, Animal; Dose-Response Relationship, Drug; Fluorescent Antibody Technique, Indirect; Glutamic Acid; Kainic Acid; Male; Mice; Mice, Inbred C57BL; Mitochondria; Ophthalmic Solutions; Rabbits; Rats; Rats, Wistar; Retina; Retinal Diseases; Retinal Ganglion Cells; Time Factors; Ubiquinone; Vitamins

Partial bladder outlet obstruction (PBOO) in rabbits causes free radical production through ischemia and reperfusion within the bladder smooth muscle and mucosa. We had previously shown that pretreatment of rabbits with a combination of α-lipoic acid (αLA) and coenzyme Q10 (CoQ) protected the bladder from contractile and metabolic dysfunctions mediated by PBOO. In this study, we examined the ability of pretreatment with αLA and CoQ combination in rabbits to protect the bladder from contractile damage mediated by either hydrogen peroxide (H(2)O(2)) or in vitro ischemia-reperfusion (I/R) which represents two in vitro models of oxidative damage.. Eight adult male New Zealand white rabbits were pretreated with CoQ and αLA orally for four weeks. Eight adult male control rabbits were given vehicle. Eight full-thickness bladder strips were isolated from each of 4 treated and 4 control rabbit bladders, and a dose-response curve to H(2)O(2) (0.1-0.8%) was generated. Similarly, isolated strips of bladder from the remaining 4 control and 4 treated rabbits were subjected to 1 h of ischemia (no oxygen without glucose) followed by 2 h of incubation in oxygenated buffer with glucose. The effects on the contractile responses to field stimulation (FS) at 2, 8, and 32 Hz, carbachol, and potassium chloride (KCl) were determined.. H(2)O(2) reduced the contractile responses to KCl and carbachol to a significantly greater degree than to FS, whereas I/R reduced the contractile responses to FS to a significantly greater degree than to KCl and carbachol. Pretreatment of the rabbits with the combination of CoQ and αLA significantly protected the bladder from the damaging effects of I/R, but had virtually no effect on the damaging effects of H(2)O(2).. Although both H(2)O(2) and I/R are in vitro models of oxidative free radical damage to bladder smooth muscle, they have significantly different methods of action and different sensitivities to antioxidants.

Topics: Animals; Antioxidants; Disease Models, Animal; Drug Therapy, Combination; Follow-Up Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Muscle Contraction; Muscle, Smooth; Oxidative Stress; Rabbits; Reperfusion Injury; Thioctic Acid; Ubiquinone; Urinary Bladder Neck Obstruction; Vitamins

The muscular dystrophies (MDs) are genetic disorders of muscle degeneration due to mutations in genes that encode a wide variety of proteins. Dysferlinopathy are characterized by the absence of dysferlin in skeletal muscle and an autosomal recessive mode of inheritance. Both histological and ultrastructural pathology have been well established in dysferlinopathy patients and dysferlin-deficient animal models. To our knowledge the effect of antioxidant supplementation on this level has not been described previously. This article therefore focuses on the histopathology to reveal the effect of antioxidant supplementation. The study aimed to determine, at cellular level, the histopathological changes in the SJL/J mouse model following a 90 day trial with antioxidant supplementation. Markedly reduced inflammatory insult in the more affected quadriceps muscles of animals treated with high doses of CoQ10 and a combination of resveratrol/CoQ10 were observed. The outcome provides evidence that high doses of antioxidant supplementation resulted in decreased dystrophic markers and enhanced tissue integrity at cellular level.

Topics: Animals; Antioxidants; Disease Models, Animal; Female; Mice; Muscle, Skeletal; Muscular Dystrophies; Resveratrol; Stilbenes; Ubiquinone

Head trauma is one of the most important clinical issues that not only can be fatal and disabling, requiring long-term treatment and care, but also can cause heavy financial burden. Formation or distribution of free oxygen radicals should be decreased to enable fixing of poor neurological outcomes and to prevent neuronal damage secondary to ischemia after trauma. Coenzyme Q₁₀ (CoQ₁₀), a component of the mitochondrial electron transport chain, is a strong antioxidant that plays a role in membrane stabilization. In this study, the role of CoQ₁₀ in the treatment of head trauma is researched by analyzing the histopathological and biochemical effects of CoQ₁₀ administered after experimental traumatic brain injury in rats. A traumatic brain-injury model was created in all rats. Trauma was inflicted on rats by the free fall of an object of 450 g weight from a height of 70 cm on the frontoparietal midline onto a metal disc fixed between the coronal and the lambdoid sutures after a midline incision was carried out.. In the biochemical tests, tissue malondialdehyde (MDA) levels were significantly higher in the traumatic brain-injury group compared to the sham group (p < 0.05). Administration of CoQ₁₀ after trauma was shown to be protective because it significantly lowered the increased MDA levels (p < 0.05). Comparing the superoxide dismutase (SOD) levels of the four groups, trauma + CoQ₁₀ group had SOD levels ranging between those of sham group and traumatic brain-injury group, and no statistically significant increase was detected. Histopathological results showed a statistically significant difference between the CoQ₁₀ and the other trauma-subjected groups with reference to vascular congestion, neuronal loss, nuclear pyknosis, nuclear hyperchromasia, cytoplasmic eosinophilia, and axonal edema (p < 0.05).. Neuronal degenerative findings and the secondary brain damage and ischemia caused by oxidative stress are decreased by CoQ₁₀ use in rats with traumatic brain injury.

Topics: Animals; Brain Injuries; Brain Ischemia; Chromatography, High Pressure Liquid; Disease Models, Animal; Neurons; Rats; Ubiquinone; Vitamins

Conventional antiepileptic drugs fail to adequately control seizures and predispose to cognitive impairment and oxidative stress with chronic usage in a significant proportion of patients with epilepsy. Coenzyme Q10 (CoQ10), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. To evaluate the neuroprotective effects of CoQ10 in rats against the observed oxidative stress during seizures induced by pilocarpine, and to study its interactions with the conventional antiepileptic drug phenytoin, two experiments were performed. Experiment 1 was conducted to test the effect of phenytoin, CoQ10, or both on seizure severity and oxidative markers in the pilocarpine model of epilepsy. Experiment 2 was conducted to test the effect of 2 weeks of chronic treatment with phenytoin, CoQ10, or both on oxidative markers and behavioral tests in rats. Overall, CoQ10 reduced the severity of pilocarpine-induced seizures and the severity of oxidative stress. Moreover, it potentiated the antiepileptic effects afforded by phenytoin treatment, with the potential safety and efficacy in ameliorating oxidative stress and cognitive impairment caused by chronic phenytoin therapy. Our findings strongly suggest that CoQ10 can be considered a safe and effective adjuvant to phenytoin therapy in epilepsy both to ameliorate seizure severity and to protect against seizure-induced oxidative damage by reducing the cognitive impairment and oxidative stress associated with chronic use of phenytoin.

Topics: Analysis of Variance; Animals; Anticonvulsants; Avoidance Learning; Catalase; Cognition Disorders; Disease Models, Animal; Drug Synergism; Glutathione; Lipid Peroxidation; Male; Malondialdehyde; Oxidative Stress; Phenytoin; Pilocarpine; Psychomotor Performance; Rats; Rats, Wistar; Reaction Time; Severity of Illness Index; Status Epilepticus; Superoxide Dismutase; Ubiquinone

In this experimental study, we assessed the preventive effects of coenzyme Q(10) (CoQ(10)) in a rat model of ischemia/reperfusion injury. The results of this study show that CoQ(10) administration before the reperfusion period of testicular torsion provides a significant decrease in testicular lipid peroxidation products and expressions of inducible nitric oxide synthase, endothelial nitric oxide synthase, and germ cell-specific apoptosis.

Topics: Animals; Apoptosis; Disease Models, Animal; Down-Regulation; Lipid Peroxidation; Male; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Rats; Rats, Wistar; Reperfusion Injury; Spermatic Cord Torsion; Testis; Ubiquinone

We previously reported that coenzyme Q10 (CoQ10) could reduce intracellular deposition in an aged transgenic mouse model. Here, we further tested the effect of CoQ10 on amyloid plaque in an amyloid precursor protein/presenilin 1 transgenic mouse model of Alzheimer's disease (AD). By using immunohistochemistry and magnetic resonance imaging to determine the burden of amyloid plaque, we found that oral administration of CoQ10 can efficiently reduce the burden of the plaques in this mouse model. These data demonstrate that in addition to reducing intracellular deposition of Abeta, CoQ10 can also reduce plaque pathology. Our study further supports the use of CoQ10 as a therapeutic candidate for AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Cerebral Cortex; Disease Models, Animal; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Mice; Mice, Transgenic; Neuroprotective Agents; Plaque, Amyloid; Presenilin-1; Ubiquinone; Vitamins

Dietary coenzyme Q10 reduces spontaneous atherosclerosis in the apoE-deficient mouse model of experimental atherosclerosis. We have shown previously that exposure to sidestream cigarette smoke (SSCS) enhances atherosclerotic lesion formation in apoE-deficient mice. The aim of the present study was to determine if CoQ10 protected against SSCS-mediated atherosclerosis. Female apoE-deficient mice were fed a saturated fat-enriched diet (SFD) alone, or supplemented with 1% wt/wt coenzyme Q10 (SFD-Q10). Mice in each diet group were exposed to SSCS for 4hrs/day, 5days/week in a whole-body exposure chamber maintained at 35+/-4mg smoke particulates/m(3). Mice kept in filtered ambient air served as controls. Mice were euthanized after either 6 or 15weeks of SSCS exposure and following measurements were performed: i) lung 7-ethoxyresorufin-O-deethylase (EROD) activity; ii) plasma cholesterol and CoQ10 concentrations; iii) aortic intimal area covered by atherosclerotic lesions; and, iv) pathological characterization of lesions. Lung EROD activity increased in SSCS mice of both diet groups, confirming SSCS exposure. Plasma concentrations of CoQ10 in SFD-Q10-fed mice were increased markedly in comparison to SFD-fed mice. Plasma cholesterol concentrations and distributions of cholesterol in lipoprotein fractions were unaffected by SSCS exposure. Dietary supplementation with CoQ10 significantly reduced atherosclerotic lesions in control mice. As reported previously, exposure to SSCS increased the size of lesions in apoE-/- mice at both time points. However, dietary supplementation with CoQ10 had no effect on atherosclerotic lesions augmented by SSCS exposure. The results suggest a role of oxidative processes in smoke-augmented atherosclerosis that are different than those mitigated by CoQ10.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Cholesterol; Cytochrome P-450 CYP1A1; Diet; Disease Models, Animal; Female; Lung; Mice; Smoke; Ubiquinone

Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington's disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition.

Topics: Animals; Anti-Bacterial Agents; Behavior, Animal; Body Weight; Disease Models, Animal; Female; Hand Strength; Huntington Disease; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Minocycline; Motor Skills; Ubiquinone

Krabbe disease or globoid cell leukodystrophy is an autosomal recessively inherited disorder caused by the deficiency of galactocerebrosidase, the lysosomal enzyme that catalyzes the hydrolysis of galactose from galactosylceramide and galactosylsphingosine (psychosine). Psychosine accumulation results in the loss of myelin and oligodendrocytes in the brain of Krabbe patients as well as twitcher mice (natural model of human Krabbe disease). The aim of the present research was to investigate in twitcher mice the potential role of a diet deficient in galactose enriched in soy isoflavones and a pool of antioxidants molecules, such as l-glutathione, coenzyme Q10, xanthophylls, in counteracting the toxic effects derived by psychosine accumulation. A second goal of this manuscript was to demonstrate suppression of the apoptotic effects of psychosine in cultured oligodendrocyte progenitor mice cells (OLP-II) with antioxidants. The affected twitcher mice began the milk-derivatives free diet on post-natal day 15 although they also received mother's milk until post-natal day 18. Nevertheless, average life span was increased 50%, from 32+/-2 to 48+/-3 days, onset of tremor was delayed 17 days (from 21 days in the untreated twitcher mice to 38 days in the treated affected mice) and the gait in the treated mice was normal until almost a week after the untreated animals died (38+/-1 days versus 32 days at death). Weight gain in the treated animals also progressed to 38 days compared with 22 days for the untreated affected twitcher mice. Protection of the OLP-II cells against psychosine was shown using the MTT test (the ability of the tetrazolium salt MTT to form a dark blue formazan product by mitochondrial dehydrogenase in viable cells) and assay of expression of p53 and TNF-related apoptosis-inducing ligand (TRAIL). The results showed a time-dependent and concentration-dependent decrease of OLP-II viability on exposure to psychosine and dose-dependent protection with the antioxidants xanthophylls and glutathione. They also demonstrated that psychosine-induced p53 induction of apoptosis and TNF-related apoptosis-inducing ligand receptors could be decreased by l-glutathione and xanthophylls. A dietary approach may constitute a promising clinical management of the late-infantile and juvenile forms of Krabbe leukodystrophy.

Topics: Animals; Antioxidants; Apoptosis; Cell Survival; Cells, Cultured; Disease Models, Animal; Female; Galactose; Glutathione; Humans; Isoflavones; Leukodystrophy, Globoid Cell; Male; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Oligodendroglia; Psychosine; Ubiquinone; Xanthophylls

This study tests the hypothesis that statins (HMGCoA reductase inhibitors) inhibit carcinogenesis and that this effect may be mediated by the statin-induced inhibition of ubiquinone synthesis.. The effects of lovastatin, with and without addition of ubiquinone, were studied in a rat model for chemically induced hepatocarcinogenesis. Intermediates in the mevalonate pathway were measured.. Lovastatin treatment reduced the volume fraction of liver nodules by 50% and the cell proliferation within the liver nodules was reduced to one third. Ubiquinone (Q10) treatment reversed the statin-induced inhibition of cell proliferation. Lathosterol levels were reduced significantly in the statin-treated rats, indicating inhibition of the mevalonate pathway, but cholesterol levels were not affected.. Lovastatin inhibits carcinogenesis in a rat model for liver cancer, despite unaffected cholesterol levels. The statin-induced inhibition of cell proliferation may, at least in part, be explained by the inhibition of ubiquinone synthesis.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Body Weight; Cell Growth Processes; Cholesterol; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver; Liver Neoplasms, Experimental; Lovastatin; Male; Mevalonic Acid; Organ Size; Precancerous Conditions; Rats; Rats, Inbred F344; Ubiquinone

Ischaemia-reperfusion injury is a life-threatening complication of lung transplantation. Attempts to ameliorate this injury have included optimization of donor management and improving techniques of lung preservation. However, few investigators have sought to pretreat potential recipients. Coenzyme Q(10) (CoQ(10)) is a potent antioxidant and cellular energizer that has been shown to protect the heart against injury. However, its protective effect in the lung is unknown. We therefore set out to study the impact of Coenzyme Q(10) pretreatment in a model of mild and severe lung injury.. We evaluated the impact of CoQ(10) in a two-stage laboratory study. In the first stage, in order to measure the magnitude of increase in tissue and plasma CoQ(10) following oral therapy we administered high-dose oral CoQ(10) to rats (n = 6). In the second stage we evaluated the impact of CoQ(10) in the rat lung (n = 10) that was subjected to 230 min of normoxic lung injury or 90 min of warm ischaemia and 120 min of reperfusion in a model of lung transplantation.. High-dose oral CoQ(10) for 7 days produced a 15-fold increase in plasma and a 3-fold increase in lung CoQ(10). In the normoxic lung, the injury-induced rise in peak airway pressure was reduced by CoQ(10) treatment at 90 min (P = 0.037) and at 120 min (P = 0.005) without any change in arterial oxygen. In the lung subjected to severe ischaemia-reperfusion injury, CoQ(10) did not reduce the injury-induced increase in peak airway pressure (P = 0.599) nor the decrease in arterial oxygen (P = 0.844). However, CoQ(10) markedly reduced the increase in tumour necrosis factor-alpha in ischaemic compared with normoxic lung (P = 0.027).. The effect of CoQ(10) pretreatment is insufficient to protect the lung against severe ischaemia-reperfusion as may occur in lung transplantation. However, in the setting of less severe pulmonary injury as in anaesthesia and non-transplant surgery, CoQ(10) may have a protective role.

Topics: Administration, Oral; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Lung; Lung Injury; Lung Transplantation; Male; Protective Agents; Rats; Reference Values; Reperfusion Injury; Treatment Outcome; Ubiquinone

Topics: Animals; Biomarkers; Disease Models, Animal; Dogs; Fluorobenzenes; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Ubiquinone

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl transferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction.

Topics: Acoustic Stimulation; Analysis of Variance; Animals; Apoptosis; Auditory Threshold; Caspase 3; Cell Count; Disease Models, Animal; Guinea Pigs; Hair Cells, Auditory, Outer; Hearing Loss, Noise-Induced; In Situ Nick-End Labeling; Microscopy, Confocal; Microscopy, Electron, Scanning; Solubility; Ubiquinone; Water

One cellular consequence of status epilepticus is apoptosis in the hippocampal CA3 subfield. We evaluated the hypothesis that the repertoire of cellular events that underlie such elicited cell death entails mitochondrial dysfunction induced by an excessive production of nitric oxide synthase II (NOS II)-derived NO, increased superoxide anion (O(2)(-)) production, and peroxynitrite formation.. In Sprague-Dawley rats, kainic acid was microinjected unilaterally into the hippocampal CA3 subfield to induce bilateral seizure-like electroencephalography (EEG) activity. The effects of pretreatments with various test agents on the induced O(2)(-) production, peroxynitrite formation, mitochondrial respiratory chain enzyme activities, cytochrome c/caspase-3 signaling, and DNA fragmentation in bilateral CA3 subfields were examined.. Significantly and temporally correlated increase in O(2)(-) and peroxynitrite levels (3 to 24 h), depressed mitochondrial Complex I activity (3 h), enhanced translocation of cytochrome c to cytosol (day 1), and augmented activated caspase-3 (day 7) and DNA fragmentation (day 7) were detected bilaterally in hippocampal CA3 subfields after the elicitation of sustained seizure. Pretreatment with microinjection into the bilateral hippocampal CA3 subfield of a water-soluble formulation of coenzyme Q(10); a selective NOS II inhibitor, S-methylisothiourea; a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; an active peroxynitrite decomposition catalyst, 5,10, 15,20-tetrakis-(N-methyl-4-pyridyl)- porphyrinato iron (III); or a peroxynitrite scavenger, L-cysteine significantly blunted these cellular events.. Prolonged seizures prompted NO-, O(2)(-)-, and peroxynitrite-dependent reduction in mitochondrial respiratory enzyme Complex I activity, leading to cytochrome c/caspase-3-dependent apoptotic cell death in the hippocampal CA3 subfield after induction of experimental temporal lobe status epilepticus.

Topics: Analysis of Variance; Animals; Apoptosis; Caspase 3; Disease Models, Animal; DNA Fragmentation; Electroencephalography; Electron Transport Complex III; Enzyme Activation; Enzyme Inhibitors; Epilepsy, Temporal Lobe; Hippocampus; Kainic Acid; Male; Mitochondria; NAD; Nitric Oxide; Peroxynitrous Acid; Phosphopyruvate Hydratase; Rats; Rats, Sprague-Dawley; Signal Transduction; Superoxides; Time Factors; Ubiquinone

Coenzyme Q(10) (CoQ(10)) and creatine are promising agents for neuroprotection in neurodegenerative diseases via their effects on improving mitochondrial function and cellular bioenergetics and their properties as antioxidants. We examined whether a combination of CoQ(10) with creatine can exert additive neuroprotective effects in a MPTP mouse model of Parkinson's disease, a 3-NP rat model of Huntington's disease (HD) and the R6/2 transgenic mouse model of HD. The combination of the two agents produced additive neuroprotective effects against dopamine depletion in the striatum and loss of tyrosine hydroxylase neurons in the substantia nigra pars compacta (SNpc) following chronic subcutaneous administration of MPTP. The combination treatment resulted in significant reduction in lipid peroxidation and pathologic alpha-synuclein accumulation in the SNpc neurons of the MPTP-treated mice. We also observed additive neuroprotective effects in reducing striatal lesion volumes produced by chronic subcutaneous administration of 3-NP to rats. The combination treatment showed significant effects on blocking 3-NP-induced impairment of glutathione homeostasis and reducing lipid peroxidation and DNA oxidative damage in the striatum. Lastly, the combination of CoQ(10) and creatine produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice. These findings suggest that combination therapy using CoQ(10) and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson's disease and HD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 8-Hydroxy-2'-Deoxyguanosine; alpha-Synuclein; Analysis of Variance; Animals; Chromatography, High Pressure Liquid; Creatine; Deoxyguanosine; Disease Models, Animal; Dopamine; Drug Therapy, Combination; Glutathione; Glutathione Disulfide; Huntington Disease; Lipid Peroxidation; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Nitro Compounds; Parkinson Disease; Propionates; Rats; Rats, Inbred Lew; Tyrosine 3-Monooxygenase; Ubiquinone

Cardiovascular alterations and periodontal disease have been associated, although cardiovascular disease treatments have not yet been tested against periodontal alterations. We investigated effects of squalene, hydroxytyrosol and coenzyme Q(10) on gingival tissues of rabbits fed on an atherosclerotic diet. Forty-eight rabbits were distributed in six groups. Control group was fed on standard chow for 80 days. The rest were fed with an atherogenic diet for 50 days. After that, a group was sacrificed and the rest were subjected for another extra 30 days on commercial chow alone or supplemented with coenzyme Q(10), squalene or hydroxytyrosol. Atherosclerotic rabbits had higher fibrosis and endothelial activation and lower cellularity in gingival mucosa than controls (P<0.05). Hydroxytyrosol reduced endothelial activation (P<0.05) and squalene additionally decreased fibrosis (P<0.05). Results suggest that gingival vascular changes after the atherosclerotic diet have been reversed by hydroxytyrosol and squalene, natural products from the minor fraction of virgin olive oil.

Topics: Animals; Antioxidants; Arteries; Atherosclerosis; Collagen; Diet, Atherogenic; Disease Models, Animal; Drug Therapy, Combination; Endothelium, Vascular; Fibrosis; Gingiva; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mouth Mucosa; Olive Oil; Periodontal Diseases; Phenylethyl Alcohol; Plant Oils; Rabbits; Squalene; Ubiquinone

Mitochondria are a major site of reactive oxygen species production, which may contribute to the development of cardiovascular disease. Protecting mitochondria from oxidative damage should be an effective therapeutic strategy; however, conventional antioxidants are ineffective, because they cannot penetrate the mitochondria. This study investigated the role of mitochondrial oxidative stress during development of hypertension in the stroke-prone spontaneously hypertensive rat, using the mitochondria-targeted antioxidant, MitoQ(10). Eight-week-old male stroke-prone spontaneously hypertensive rats were treated with MitoQ(10) (500 mumol/L; n=16), control compound decyltriphenylphosphonium (decylTPP; 500 mumol/L; n=8), or vehicle (n=9) in drinking water for 8 weeks. Systolic blood pressure was significantly reduced by approximately 25 mm Hg over the 8-week MitoQ(10) treatment period compared with decylTPP (F=5.94; P=0.029) or untreated controls (F=65.6; P=0.0001). MitoQ(10) treatment significantly improved thoracic aorta NO bioavailability (1.16+/-0.03 g/g; P=0.002, area under the curve) compared with both untreated controls (0.68+/-0.02 g/g) and decylTPP-treated rats (0.60+/-0.06 g/g). Cardiac hypertrophy was significantly reduced by MitoQ(10) treatment compared with untreated control and decylTPP treatment (MitoQ(10): 4.01+/-0.05 mg/g; control: 4.42+/-0.11 mg/g; and decylTPP: 4.40+/-0.09 mg/g; ANOVA P=0.002). Total MitoQ(10) content was measured in liver, heart, carotid artery, and kidney harvested from MitoQ(10)-treated rats by liquid chromatography-tandem mass spectrometry. All of the organs analyzed demonstrated detectable levels of MitoQ(10), with comparable accumulation in vascular and cardiac tissues. Administration of the mitochondria-targeted antioxidant MitoQ(10) protects against the development of hypertension, improves endothelial function, and reduces cardiac hypertrophy in young stroke-prone spontaneously hypertensive rats. MitoQ(10) provides a novel approach to attenuate mitochondrial-specific oxidative damage with the potential to become a new therapeutic intervention in human cardiovascular disease.

Topics: Analysis of Variance; Animals; Antioxidants; Blood Pressure; Cardiomegaly; Disease Models, Animal; Drug Delivery Systems; Endothelium, Vascular; Hypertension; Male; Membrane Potential, Mitochondrial; Mitochondria; Oxidative Stress; Probability; Random Allocation; Rats; Rats, Inbred SHR; Risk Factors; Sensitivity and Specificity; Ubiquinone

This work aimed to assess some pharmacological activities of coenzyme Q(10) (CoQ(10)) in animal experimental models.. The chick chorioallantoic membrane assay was used to evaluate anti-angiogenic activity of CoQ(10). Anti-inflammatory activity of CoQ(10) was confirmed using two animal models of inflammation. These were the vascular permeability and air pouch models, models of acute and sub-acute inflammation, respectively. Antinociceptive activity was assessed by the acetic acid-induced abdominal constriction response.. CoQ(10) dose-dependently displayed inhibition of chick chorioallantoic membrane angiogenesis. In the acetic acid-induced vascular permeability model in mice, CoQ(10) at 50, 100 and 200 mg/kg reduced vascular permeability from 0.74 +/- 0.01 (A(590)) to 0.67 +/- 0.01 (P < 0.01), 0.46 +/- 0.02 (P < 0.01) and 0.30 +/- 0.01 (P < 0.01), respectively. In the carrageenan-induced inflammation in the air pouch, CoQ(10) was able to diminish exudate volume, the number of polymorphonulcear leucocytes and nitrite content in the air pouches. CoQ(10) at 25, 50 and 100 mg/kg significantly reduced acetic acid-induced abdominal constriction in mice from 27.0 +/- 2.00 (number of abdominal constrictions) to 17.7 +/- 0.33 (P < 0.01), 9.3 +/- 0.67 (P < 0.01) and 1.3 +/- 0.33 (P < 0.01), respectively, suggesting a strong antinociceptive activity.. CoQ(10) possessed considerable anti-angiogenic, anti-inflammatory and antinociceptive activity, possibly via down-regulating the level of nitric oxide, which partly supported its use as a dietary supplement and in combination therapy.

Topics: Abdominal Pain; Analgesics; Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Capillary Permeability; Chick Embryo; Chorioallantoic Membrane; Disease Models, Animal; Dose-Response Relationship, Drug; Exudates and Transudates; Inflammation; Male; Mice; Mice, Inbred ICR; Neovascularization, Physiologic; Nitrites; Ubiquinone; Vitamins

Metabolic syndrome (MetS) is a group of cardiovascular risk factors, including visceral obesity, glucose intolerance, hypertension, and dyslipidemia. Increased oxidative and nitrative stress and inflammation and decreased endothelial function occur in an animal model of metabolic syndrome, SHR/NDmcr-cp (SHR/cp) rats. The present study investigated the effects of coenzyme Q10 (CoQ10), one of the important antioxidants, on the abnormal oxidative condition and characteristic components of metabolic syndrome in SHR/cp rats by maintaining them on a diet supplemented with 0.07% - 0.7% CoQ10 for 26 weeks. We determined serum levels of oxidatively modified low-density lipoprotein (Ox-LDL) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as oxidative stress markers, 3-nitrotyrosine as a nitrative stress marker, 3-chlorotyrosine as a marker of myeloperoxidase (MPO)-catalyzed oxidation and high-sensitivity C-reactive protein (hsCRP) as an inflammatory marker. The administration of CoQ10 significantly attenuated the increase of oxidative and nitrative stress markers and inflammatory markers in a dose-dependent manner. CoQ10 prevented the elevated serum insulin levels, although it did not affect the elevated glucose level and dyslipidemia. CoQ10 also reduced elevated blood pressure, but did not affect body weight gain. In addition, CoQ10 improved endothelial dysfunction in the mesenteric arteries. These findings suggest that the antioxidant properties of CoQ10 can be effective for ameliorating cardiovascular risk in MetS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Body Weight; Deoxyguanosine; Disease Models, Animal; Inflammation; Insulin; Lipids; Lipoproteins, LDL; Metabolic Syndrome; Oxidative Stress; Peroxidase; Rats; Rats, Inbred SHR; Tyrosine; Ubiquinone

Inhibition of squalene synthesis could transform unstable, macrophage/lipid-rich coronary plaques into stable, fibromuscular plaques. We have here treated WHHLMI rabbits, a model for coronary atherosclerosis and myocardial infarction, with a novel squalene synthase inhibitor, lapaquistat acetate (TAK-475).. Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly.. Lapaquistat acetate decreased plasma cholesterol and triglyceride levels, by lowering lipoproteins containing apoB100. Development of atherosclerosis and xanthomatosis was suppressed. Accumulation of oxidized lipoproteins, macrophages and extracellular lipid was decreased in coronary plaques of treated animals. Treatment with lapaquistat acetate increased collagen concentration and transformed coronary plaques into fibromuscular plaques. Lapaquistat acetate also suppressed the expression of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 in the plaque and increased peripheral coenzyme Q10 levels. Increased coenzyme Q10 levels and decreased very low-density lipoprotein cholesterol levels were correlated with improvement of coronary plaque composition.. Inhibition of squalene synthase by lapaquistat acetate delayed progression of coronary atherosclerosis and changed coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions.

Topics: Animals; Apolipoprotein B-100; Cholesterol; Collagen; Coronary Artery Disease; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Enzyme Inhibitors; Farnesyl-Diphosphate Farnesyltransferase; Hypercholesterolemia; Hypolipidemic Agents; Image Interpretation, Computer-Assisted; Immunohistochemistry; Lipid Metabolism; Lipoproteins, LDL; Macrophages; Male; Matrix Metalloproteinase 1; Oxazepines; Piperidines; Plasminogen Activator Inhibitor 1; Rabbits; Triglycerides; Ubiquinone; Xanthomatosis

We studied the influence of antioxidants (trolox, melatonin and coenzyme Q10) on 6-hydroxydopamine-induced degeneration in the substantia nigra dopaminergic neurons from the left brain hemisphere. In rats, the level of unilateral degeneration of nigrostriatal dopaminergic system was estimated on the base of an intensity of rotation movements which were contralateral to denervated hemishere and resulted from systemic injections of a dopamine receptor agonist apomorphine. It has been shown that all tested antioxidants reduced a number of animals with apomorphine-induced behavioral asymmetry in a different degree: coenzyme Q10 reduced it twofold, trolox - fivefold and melatonin - sevenfold. We suggest that a neuroprotective effects of trolox, melatonin and coenzyme Q10 are associated with their ability to block the mitochondrial pore openings in the nervous cells under exploration, and this is the way to prevent apoptotic death. An oxidative stress has been proved to take part in the apoptosis in dopamine-producing neurons in the substantia nigra, and tested antioxidants have been shown to be effective in preventing neurodegeneration.

Topics: Animals; Antioxidants; Behavior, Animal; Chromans; Disease Models, Animal; Dopamine; Male; Melatonin; Neurons; Oxidative Stress; Oxidopamine; Parkinsonian Disorders; Rats; Rats, Inbred WKY; Substantia Nigra; Ubiquinone

Recent evidence indicates that ischemia and reperfusion are major etiological factors in the bladder dysfunction that occurs after partial bladder outlet obstruction. Coenzyme Q10 and alpha-lipoic acid are found naturally in mitochondria and act as potent antioxidants. We investigated the beneficial effects of coenzyme Q10 plus alpha-lipoic acid in a rabbit model of bladder outlet obstruction.. Twenty male rabbits were divided into 5 groups. Group 1 served as control and group 2 received three weeks of coenzyme Q10 plus alpha-lipoic acid supplementation. Rabbits in group 3 underwent surgical partial bladder outlet obstruction for duration of four weeks and groups 4 and 5 were obstructed for seven weeks. In group 5, coenzyme Q10 plus alpha-lipoic acid supplementation was given following 4 weeks obstruction and continued till the end of the seven weeks. The contractile responses to various agents were determined. The protein nitration and carbonylation levels were studied by immunoblotting. Nerve function was determined by choline acetyltransferase activity and nerve density.. The contractile responses to different forms of stimulations, including field stimulation, ATP, carbachol and KCl all showed decreases following 4 and 7 weeks obstruction. Treatment with coenzyme Q10 plus alpha-lipoic acid significantly restored contractile responses to all forms of stimulation. Treatment also had mitochondrial and neuronal effects and reduced protein nitration and carbonylation. Histologically there was less detrusor muscle hypertrophy.. The current study clearly demonstrates that coenzyme Q10 and alpha-lipoic acid supplementation can improve bladder function after outlet obstruction.

Topics: Analysis of Variance; Animals; Blotting, Western; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Immunohistochemistry; Male; Muscle Contraction; Muscle, Smooth; Probability; Rabbits; Random Allocation; Sensitivity and Specificity; Thioctic Acid; Ubiquinone; Urinary Bladder Neck Obstruction

Current treatment options for parkinsonism as a neurodegenerative disease are limited and still mainly symptomatic and lack significant disease-modifying effect. Understanding its molecular pathology and finding the cause of dopaminergic cell loss will lead to exploring therapies that could prevent and cure the disease. Mitochondrial dysfunction was found to stimulate releasing of reactive oxygen species (ROS) with subsequent induction of apoptotic neuronal cell death. The aim of the present study was to throw the light on the role of coenzyme Q10 with or without L-dopa in an experimental model of parkinsonism induced by rotenone in rats. The present work showed that rotenone (2.5 mg/kg/day i.p. for 60 days) induced a model of parkinsonism (group II) resembling the basic findings in human characterized by bradykinesia and rigidity manifested as an increase in catalepsy score (detected after 20 days with bad prognosis after 60 days) with marked decrease in striatal dopamine levels. This model confirmed the implication of mitochondrial-apoptotic pathway in the pathogenesis of parkinsonism as there was a decrease in levels of striatal complex I activity and ATP as well as extreme overexpression of the antiapoptotic protein Bcl-2, and also exhibited the role of coenzyme Q10 where its plasma and striatal levels were found to be decreased in comparison to the normal control rats (group I). This proposed pathogenesis was evidenced by the significant correlation between catalepsy score and the neurochemical parameters obtained in the current work. The treated groups started to receive the drug(s) after 20 days from induction of parkinsonism and continued to complete for 60 days. Oral administration of Co Q10 in a low dose 200 mg/kg/day (group III) or a high dose 600 mg/kg/day (group IV), resulted in amelioration of the mitochondrial induced apoptosis by dose-dependent restoration of striatal complex I activity, ATP levels with temperate increase in expression of Bcl-2 as well as decrease in catalepsy score. Although both low and high doses of Co Q10 resulted in significant increase in its plasma and striatal levels, but only the high dose was shown to reach the recommended therapeutic levels. As a current replacement therapy, oral administration of levodopa 10 mg/kg/day (group V), caused symptomatic improvement in the form of reduction of catalepsy score with restoration of striatal dopamine levels, but it did not show any significant effects on either striatal c

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Antiparkinson Agents; Behavior, Animal; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Levodopa; Mitochondria; NAD; Neurons; Parkinsonian Disorders; Proto-Oncogene Proteins c-bcl-2; Psychomotor Performance; Rats; Rotenone; Spectrophotometry; Ubiquinone; Ultrasonography; Vitamins

This study was designed to determine whether the supplement of energy compound could attenuate strain-induced damage to skeletal muscle in rats. Energy compound is a saline mixture of the following ingredients: ATP (10mg), Coenzyme-A (50 units), Coenzyme-Q(10) (50mg), Cytochrome C (30 mg) and Vitamin B(6) (50mg). Experimental animals were injured in right gastrocnemius muscles by a strain injury model. Energy compound groups were given energy compound 10 ml/kg body weight per day since injured, while saline groups were given saline at the same dose. And a sham operation was performed on the right hindlimb of control group. Plasma was centrifuged to measure lactate dehydrogenase (LDH), lactic acid (La) and creatine kinase (CK) on 3, 7 and 14 d post injury. Muscles were removed and fixed for histology observation and immunohistochemistry assay of desmin and vimentin. The results showed a similar tendency of plasma CK, La and LDH in saline and energy compound groups, while the lower level was found in the energy-compound group. The histological examination of muscle sections revealed a lower degree of damage in the energy compound group in which the expression levels of desmin and vimentin were higher than in the saline group. It is suggested that energy compound supplement may attenuate strain-induced muscle damage and facilitate its regeneration.

Topics: Adenosine Triphosphate; Animals; Coenzyme A; Cytochromes c; Disease Models, Animal; Energy Metabolism; Male; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Sprains and Strains; Ubiquinone; Vitamin B 6; Wound Healing

The importance of nutritional supplementation in diabetes remains an unresolved issue. The present study was undertaken to examine the effects of alpha-tocopherol and CoQ(10), powerful antioxidants, on metabolic control and on the pancreatic mitochondria of GK rats, a model of type 2 diabetes. We also evaluated the efficacy of these nutrients in preventing the diabetic pancreatic lesions observed in GK rats. Rats were divided into 4 groups, a control group of diabetic GK rats and 3 groups of GK rats administered with alpha-tocopherol and CoQ(10) alone or both in association, during 8 weeks. Fasting blood glucose levels were not significantly different between the groups, nor were blood glucose levels at 2 hours after a glucose load. HbA1c level was significantly reduced in the group supplemented with both antioxidants. Diabetes induced a decrease in coenzyme Q plasma levels that prevailed after treatment with antioxidants. In addition, the plasma alpha-tocopherol levels were higher after treatment with the antioxidants. An increment in some components of the antioxidant defense system was observed in pancreatic mitochondria of treated GK rats. Moreover, the antioxidants tested either alone or in association failed to prevent the pancreatic lesions in this animal model of type 2 diabetes. In conclusion, our results indicate that CoQ(10) and alpha-tocopherol decrease glycated HbA1c and pancreatic lipid peroxidation. These antioxidants increase some components of the antioxidant defense system but do not prevent pancreatic lesions. Thus, we cannot rule out the potential benefit of antioxidant treatments in type 2 diabetes in the prevention of their complications.

Topics: alpha-Tocopherol; Animals; Antioxidants; Blood Glucose; Diabetes Mellitus, Experimental; Dietary Supplements; Disease Models, Animal; Glucose Tolerance Test; Glycated Hemoglobin; Insulin; Lipid Peroxidation; Male; Pancreas; Random Allocation; Rats; Rats, Inbred Strains; Rats, Wistar; Ubiquinone

Coenzyme Q10 (CoQ10) is a promising agent for neuroprotection in neurodegenerative diseases. We tested the effects of various doses of two formulations of CoQ10 in food and found that administration in the diet resulted in significant protection against loss of dopamine (DA), which was accompanied by a marked increase in plasma concentrations of CoQ10. We further investigated the neuroprotective effects of CoQ10, reduced CoQ10 (ubiquinol), and CoQ10 emulsions in the (MPTP) model of Parkinson's disease (PD). We found neuroprotection against MPTP induced loss of DA using both CoQ10, and reduced CoQ10, which produced the largest increases in plasma concentrations. Lastly, we administered CoQ10 in the diet to test its effects in a chronic MPTP model induced by administration of MPTP by Alzet pump for 1 month. We found neuroprotective effects against DA depletion, loss of tyrosine hydroxylase neurons and induction of alpha-synuclein inclusions in the substantia nigra pars compacta. The finding that CoQ10 is effective in a chronic dosing model of MPTP toxicity, is of particular interest, as this may be more relevant to PD. These results provide further evidence that administration of CoQ10 is a promising therapeutic strategy for the treatment of PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animal Feed; Animals; Coenzymes; Disease Models, Animal; Dopamine; Drug Interactions; Male; Mice; Neurons; Neuroprotective Agents; Neurotoxins; Oxidation-Reduction; Parkinsonian Disorders; Ubiquinone; Vitamins

Oxidative stress and antioxidants play an important role in neurodegenerative diseases. However, the exact participation of antioxidants in the evolution of prion diseases is still largely unknown. The aim of this study was to assess brain levels of coenzyme Q (CoQ), an endogenous lipophilic antioxidant, and the antioxidant/pro-oxidant status by determining oxidative damage to proteins and lipids after intracerebral bovine spongiform encephalopathy (BSE) infection of transgenic mice expressing bovine prion protein (PrP). Our results indicate that, whereas the ratio between the two CoQ homologues present in mice (CoQ(9) and CoQ(10)) is not altered by prion infection during the course of the disease, significant increases in total CoQ(9) and CoQ(10) were observed in BSE-infected mice 150 days after inoculation. This time point coincided with the first manifestation of PrP(Sc) deposition in nervous tissue. In addition, CoQ(9) and CoQ(10) levels, neuropathological alterations, and PrP(Sc) deposition in nervous tissues underwent further increases as the illness progressed. Lipid and protein oxidation were observed only at the final stage of the disease after clinical signs had appeared. These findings indicate upregulation of CoQ(9)- and CoQ(10)-dependent antioxidant systems in response to the increased oxidative stress induced by prion infection in nervous tissue. However, the induction of these endogenous antioxidant systems seems to be insufficient to prevent the development of the illness.

Topics: Animals; Antioxidants; Biomarkers; Brain; Cattle; Coenzymes; Disease Models, Animal; Encephalopathy, Bovine Spongiform; Lipid Metabolism; Mice; Mice, Transgenic; Oxidation-Reduction; Oxidative Stress; Prions; PrPSc Proteins; Ubiquinone; Up-Regulation

N-acetylcysteine, beta-glucan, and coenzyme Q10 have been shown to have antioxidant and anti-inflammatory effects on reperfusion injury. The aim of our study was to determine and evaluate the effects of these agents on myocardial ischemia-reperfusion injury.. Forty-four New Zealand white rabbits, all female, weighing 2.4 to 4.1 kg (mean, 3.6 kg) were used in the study. Four study groups of 11 animals were arranged by randomization. The groups were the control group (group C), a group premedicated with coenzyme Q10 (group Q), a group premedicated with beta-glucan (group betaT), and a group premedicated with N-acetylcysteine (group N). After exploration of the heart, a basal myocardial biopsy was taken from the anteroapical left ventricle, and the first blood sampling was done before ischemia. For the ischemia-reperfusion experiments, the major left anterior descending artery was occluded after baseline measurements. After a 45-minute transient ischemic period, the heart was perfused for 120 minutes. After perfusion, the second myocardial biopsy was taken from the anteroapical left ventricle, and the second blood sampling was done. Blood and tissue analysis were performed and evaluated statistically.. Baseline and reperfusion levels of glutathione peroxidase, superoxide dismutase, malonyldialdehyde, and nitric oxide changed significantly. While malonyldialdehyde levels increased in group C, they decreased in the other study groups (P =.001). The increases in glutathione peroxidase and superoxide dismutase levels were significant in all groups except group C (P =.0001 and P <.05, respectively). Levels of nitric oxide were found to be decreased in group C, whereas they increased in the other groups (P =.001).. Antioxidant medication may help in lowering the risk of myocardial ischemia-reperfusion injury. All the medications in our study are shown to have effective roles in preventing ischemia-reperfusion injury to some extent through their antioxidant properties.

Topics: Acetylcysteine; Animals; Antioxidants; beta-Glucans; Coenzymes; Disease Models, Animal; Female; Myocardial Reperfusion Injury; Rabbits; Ubiquinone

In present research the action of coenzyme Q10 on energetic metabolism and antioxidant system at different temperature conditions has been studied. It was established that the addition of coenzyme Q10 caused inadequate stimulation of main metabolic systems that could lead to running out of functional reserves of cardiomyocytes. The use of coenzyme Q10 helped to optimize intracellular compensating mechanisms supplying the defense of myocardium. Introduction in a diet coenzyme Q10 in conditions of a temperature's comfort threshold excess and development of a histic hypoxia can promote the decrease of gravity of hypoxic myocardium's lesions and to glycogenolysis' amplification that promotes maintenance of an energy homeostasis of a myocardium in posthypoxia term. It is possible to assume, that the augmentation of duration of reception coenzyme Q10 or its dosages can render more expressed protective effect.

Topics: Adaptation, Physiological; Animals; Coenzymes; Dietary Supplements; Disease Models, Animal; Energy Metabolism; Housing, Animal; Hypoxia; Male; Myocardium; Rats; Temperature; Ubiquinone

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) have been proven to reduce effectively cholesterol level and morbidity and mortality in patients with coronary heart disease and/or dyslipoproteinemia. Statins inhibit synthesis of mevalonate, a precursor of both cholesterol and coenzyme Q (CoQ). Inhibited biosynthesis of CoQ may be involved in some undesirable actions of statins. We investigated the effect of simvastatin on tissue CoQ concentrations in the rat model of NO-deficient hypertension induced by chronic L-NAME administration. Male Wistar rats were treated daily for 6 weeks with L-NAME (40 mg/kg) or with simvastatin (10 mg/kg), another group received simultaneously L-NAME and simvastatin in the same doses. Coenzyme Q(9) and Q(10) concentrations were analyzed by high performance liquid chromatography. L-NAME and simvastatin alone had no effect on CoQ concentrations. However, simultaneous application of L-NAME and simvastatin significantly decreased concentrations of both CoQ homologues in the left ventricle and slightly decreased CoQ(9) concentration in the skeletal muscle. No effect was observed on CoQ level in the liver and brain. We conclude that the administration of simvastatin under the condition of NO-deficiency reduced the level of CoQ in the heart and skeletal muscle what may participate in adverse effect of statins under certain clinical conditions.

Topics: Animals; Brain; Coenzymes; Disease Models, Animal; Down-Regulation; Heart Ventricles; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Liver; Male; Muscle, Skeletal; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Wistar; Simvastatin; Time Factors; Ubiquinone

The neuropathological and clinical symptoms of Huntington's disease (HD) can be simulated in animal model with systemic administration of 3-nitropropionic acid (3-NP). Energy defects in HD could be ameliorated by administration of coenzyme Q(10) (CoQ(10)), creatine, or nicotinamid. We studied the activity of creatine kinase (CK) and the function of mitochondrial respiratory chain in the brain of aged rats administered with 3-NP with and without previous application of antioxidants CoQ(10)+vitamin E. We used dynamic and steady-state methods of in vivo phosphorus magnetic resonance spectroscopy ((31)P MRS) for determination of the pseudo-first order rate constant (k(for)) of the forward CK reaction, the phosphocreatine (PCr) to adenosinetriphosphate (ATP) ratio, intracellular pH(i) and Mg(i)(2+) content in the brain. The respiratory chain function of isolated mitochondria was assessed polarographically; the concentration of CoQ(10) and alpha-tocopherol by HPLC. We found significant elevation of k(for) in brains of 3-NP rats, reflecting increased rate of CK reaction in cytosol. The function of respiratory chain in the presence of succinate was severely diminished. The activity of cytochromeoxidase and mitochondrial concentration of CoQ(10) was unaltered; tissue content of CoQ(10) was decreased in 3-NP rats. Antioxidants CoQ(10)+vitamin E prevented increase of k(for) and the decrease of CoQ(10) content in brain tissue, but were ineffective to prevent the decline of respiratory chain function. We suppose that increased activity of CK system could be compensatory to decreased mitochondrial ATP production, and CoQ(10)+vitamin E could prevent the increase of k(for) after 3-NP treatment likely by activity of CoQ(10) outside the mitochondria. Results of our experiments contributed to elucidation of mechanism of beneficial effect of CoQ(10) administration in HD and showed that the rate constant of CK is a sensitive indicator of brain energy disorder reflecting therapeutic effect of drugs that could be used as a new in vivo biomarker of neurodegenerative diseases.

Topics: Adenosine Triphosphate; Animals; Brain; Coenzymes; Creatine Kinase; Disease Models, Animal; Electron Transport Complex IV; Energy Metabolism; Huntington Disease; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Oxidative Phosphorylation; Phosphocreatine; Rats; Rats, Wistar; Ubiquinone; Vitamin E

Huntington's disease (HD) is a fatal neurodegenerative disorder of genetic origin with no known therapeutic intervention that can slow or halt disease progression. Transgenic murine models of HD have significantly improved the ability to assess potential therapeutic strategies. The R6/2 murine model of HD, which recapitulates many aspects of human HD, has been used extensively in pre-clinical HD therapeutic treatment trials. Of several potential therapeutic candidates, both minocycline and coenzyme Q10 (CoQ10) have been demonstrated to provide significant improvement in the R6/2 mouse. Given the specific cellular targets of each compound, and the broad array of abnormalities thought to underlie HD, we sought to assess the effects of combined minocycline and CoQ10 treatment in the R6/2 mouse. Combined minocycline and CoQ10 therapy provided an enhanced beneficial effect, ameliorating behavioral and neuropathological alterations in the R6/2 mouse. Minocycline and CoQ10 treatment significantly extended survival and improved rotarod performance to a greater degree than either minocycline or CoQ10 alone. In addition, combined minocycline and CoQ10 treatment attenuated gross brain atrophy, striatal neuron atrophy, and huntingtin aggregation in the R6/2 mice relative to individual treatment. These data suggest that combined minocycline and CoQ10 treatment may offer therapeutic benefit to patients suffering from HD.

Topics: Animals; Anti-Bacterial Agents; Behavior, Animal; Body Weight; Coenzymes; Cytoprotection; Disease Models, Animal; Drug Therapy, Combination; Humans; Huntingtin Protein; Huntington Disease; Mice; Mice, Transgenic; Microglia; Minocycline; Nerve Tissue Proteins; Nuclear Proteins; Survival Rate; Ubiquinone

There is substantial evidence that a bioenergetic defect may play a role in the pathogenesis of Huntington's Disease (HD). A potential therapy for remediating defective energy metabolism is the mitochondrial cofactor, coenzyme Q10 (CoQ10). We have reported that CoQ10 is neuroprotective in the R6/2 transgenic mouse model of HD. Based upon the encouraging results of the CARE-HD trial and recent evidence that high-dose CoQ10 slows the progressive functional decline in Parkinson's disease, we performed a dose ranging study administering high levels of CoQ10 from two commercial sources in R6/2 mice to determine enhanced efficacy. High dose CoQ10 significantly extended survival in R6/2 mice, the degree of which was dose- and source-dependent. CoQ10 resulted in a marked improvement in motor performance and grip strength, with a reduction in weight loss, brain atrophy, and huntingtin inclusions in treated R6/2 mice. Brain levels of CoQ10 and CoQ9 were significantly lower in R6/2 mice, in comparison to wild type littermate control mice. Oral administration of CoQ10 elevated CoQ10 plasma levels and significantly increased brain levels of CoQ9, CoQ10, and ATP in R6/2 mice, while reducing 8-hydroxy-2-deoxyguanosine concentrations, a marker of oxidative damage. We demonstrate that high-dose administration of CoQ10 exerts a greater therapeutic benefit in a dose dependent manner in R6/2 mice than previously reported and suggest that clinical trials using high dose CoQ10 in HD patients are warranted.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenosine Triphosphate; Animals; Body Weight; Coenzymes; Deoxyguanosine; Disease Models, Animal; Dose-Response Relationship, Drug; Huntingtin Protein; Huntington Disease; Male; Mice; Mice, Transgenic; Neostriatum; Nerve Tissue Proteins; Neuroprotective Agents; Nuclear Proteins; Rotarod Performance Test; Treatment Outcome; Ubiquinone

Regional distribution of coenzyme Q10 and mitochondrial complex-1 activity were estimated in the brains of control-(C57BL/6), metallothionein knock out-, metallothionein transgenic-, and homozygous weaver mutant mice; and human dopaminergic (SK-N-SH) cells with a primary objective to determine the neuroprotective potential of coenzyme Q10 in Parkinson's disease. Complex-1 activity as well as coenzyme Q10 were significantly higher in the cerebral cortex as compared to the striatum in all the genotypes examined. Complex-1 activity and coenzyme Q10 were significantly reduced in weaver mutant mice and metallothionein knock out mice, but were significantly increased in metallothionein transgenic mice. The reduced complex-1 activity and 18F-DOPA uptake occurred concomitantly with negligible differences in the coenzyme Q10 between in the cerebral cortex and striatum of weaver mutant mice. Administration of coenzyme Q10 increased complex-1 activity and partially improved motoric performance in weaver mutant mice. Direct exposure of rotenone also reduced coenzyme Q10, complex-1 activity, and mitochondrial membrane potential in SK-N-SH cells. Rotenone-induced down-regulation of complex-1 activity was attenuated by coenzyme Q10 treatment, suggesting that complex-1 may be down regulated due to depletion of coenzyme Q10 in the brain. Therefore, metallothionein-induced coenzyme Q10 synthesis may provide neuroprotection by augmenting mitochondrial complex-1 activity in Parkinson's disease.

Topics: Analysis of Variance; Animals; Brain; Cell Line, Tumor; Chromatography, High Pressure Liquid; Coenzymes; Dihydroxyphenylalanine; Disease Models, Animal; Electron Transport Complex I; Fluorine Radioisotopes; Humans; Male; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Mice, Transgenic; Neuroblastoma; Neuroprotective Agents; Parkinson Disease; Positron-Emission Tomography; Statistics as Topic; Tissue Distribution; Ubiquinone

The HD-N171-82Q (line 81) mouse model of Huntington's disease (HD), expresses an N-terminal fragment of mutant huntingtin (htt), loses motor function, displays HD-related pathological features, and dies prematurely. In the present study, we compare the efficacy with which environmental, pharmacological, and genetic interventions ameliorate these abnormalities. As previously reported for the R6/2 mouse model of HD, housing mice in enriched environments improved the motor skills of N171-82Q mice. However, life expectancy was not prolonged. Significant improvements in motor function, without prolonging survival, were also observed in N171-82Q mice treated with Coenzyme Q10 (CoQ10, an energy metabolism enhancer). Several compounds were not effective in either improving motor skills or prolonging life, including Remacemide (a glutamate antagonist), Celecoxib (a COX-2 inhibitor), and Chlorpromazine (a prion inhibitor); Celecoxib dramatically shortened life expectancy. We also tested whether raising cellular antioxidant capacity by co-expressing high levels of wild-type human Cu/Zn superoxide dismutase 1 (SOD1) was beneficial. However, no improvement in motor performance or life expectancy was observed. Although we would argue that positive outcomes in mice carry far greater weight than negative outcomes, we suggest that caution may be warranted in testing Celecoxib in HD patients. The positive outcomes achieved by CoQ10 therapy and environmental stimuli point toward two potentially therapeutic approaches that should be readily accessible to HD patients and at-risk family members.

Topics: Acetamides; Animals; Celecoxib; Chlorpromazine; Coenzymes; Cyclooxygenase Inhibitors; Disease Models, Animal; Disease Progression; Dopamine Antagonists; Environment, Controlled; Female; Humans; Huntington Disease; Mice; Mice, Transgenic; Motor Activity; Motor Skills; Neuroprotective Agents; Phenotype; Pyrazoles; Sulfonamides; Superoxide Dismutase; Superoxide Dismutase-1; Survival Rate; Treatment Outcome; Ubiquinone

The effects of exogenous toxins (MPP(+), rotenone) and potentially neurotoxic properties of levodopa (L-DOPA) on the survival rate of dopaminergic neurons in dissociated primary culture are presented. Dopamine agonists show a capacity to counteract MPP(+)-toxicity. Moreover, a preserving potential of the antioxidant and bioenergetic coenzyme Q(10) (CoQ(10)) on the activities of tyrosine hydroxylase (TH), complexes I and II of the respiratory chain, and hexokinase activity in striatal slice cultures against MPP(+) is demonstrated.

Topics: Animals; Coenzymes; Disease Models, Animal; Dopamine; Dopamine Agonists; Mice; Mice, Inbred C57BL; Neurons; Neurotoxins; Oxidative Stress; Parkinson Disease; Tyrosine 3-Monooxygenase; Ubiquinone

Coenzyme Q10 (CoQ10, ubiquinone) is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an antioxidant. We evaluated the neuroprotective efficacy of CoQ10 against fatality in an experimental model of endotoxemia that mimics systemic inflammatory response syndrome using a novel water-soluble formulation of this quinone derivative. Experiments were conducted in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Intravenous administration of Escherichia coli lipopolysaccharide (LPS; 30 mg/kg) induced progressive hypotension, with death ensuing within 4 h. The sequence of cardiovascular events during this LPS-induced endotoxemia can be divided into a reduction (Phase I), followed by an augmentation (Phase II; "pro-life" phase) and a secondary decrease (Phase III; "pro-death" phase) in the power density of the vasomotor components (0-0.8 Hz) of systemic arterial pressure signals. Pretreatment by microinjection bilaterally of CoQ10 (1 or 2 microg) into the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, significantly diminished mortality, prolonged survival time, and reduced the slope or magnitude of the LPS-induced hypotension. CoQ10 pretreatment also significantly prolonged the duration of and augmented the total power density of the vasomotor components of systemic arterial pressure signals in Phase II endotoxemia. The increase in superoxide anion production induced by LPS at the RVLM during Phases II and III endotoxemia was also significantly blunted. We conclude that CoQ10 provides neuroprotection against fatality during experimental endotoxemia by reducing superoxide anion production at the RVLM, whose neuronal activity is intimately related to the "life-and-death" process.

Topics: Animals; Coenzymes; Disease Models, Animal; Endotoxemia; Escherichia coli; Lipopolysaccharides; Male; Medulla Oblongata; Microinjections; Rats; Rats, Sprague-Dawley; Superoxides; Survival Rate; Time Factors; Ubiquinone

Diabetes, which causes enhanced oxidative stress, is a multifactorial disease that leads to deleterious effects in many organ systems within the body. Ubiquinones (coenzyme Q(9) and Q(10)) are amphipathic molecular components of the electron transport chain that function also as endogenous antioxidants and attenuate the diabetes-induced decreases in antioxidant defense mechanisms. Insulin-like growth factor 1 (IGF-1) is considered to be an "essential surviving factor", the level and function of which are compromised in diabetes. This study investigated the impact of IGF-1 supplementation on ubiquinone levels in a rat model of type I diabetes. Adult male Sprague-Dawley rats were divided into four groups: control, control plus IGF-1, diabetic and diabetic plus IGF-1. Diabetic animals received a single intravenous injection of streptozotocin (STZ, 55 mg/kg). IGF-1 supplementation groups received a daily intraperitoneal dose of 3 mg IGF-1 per kilogram body weight for 7 weeks. Coenzyme Q(9) and Q(10) levels were assessed by ultraviolet detection on high pressure liquid chromatography. STZ caused a significant reduction in body weight and an elevation in blood glucose level, which were not prevented by IGF-1 supplementation. In addition Q(9) and Q(10) levels in diabetic liver were significantly elevated. IGF-1 supplementation prevented liver alterations in Q(10) but not Q(9) levels. Q(9) and Q(10) levels in diabetic kidney were significantly depressed, and these deleterious effects were abolished by IGF-1 treatment. These data suggest that IGF-1 antagonizes the diabetes-induced alterations in endogenous antioxidants including coenzyme Q(10), and hence may have a therapeutic role in diabetes.

Topics: Animals; Coenzymes; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dietary Supplements; Disease Models, Animal; Insulin-Like Growth Factor I; Kidney; Liver; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reference Values; Ubiquinone

There is substantial evidence that bioenergetic defects and excitotoxicity may play a role in the pathogenesis of Huntington's disease (HD). Potential therapeutic strategies for neurodegenerative diseases in which there is reduced energy metabolism and NMDA-mediated excitotoxicity are the administration of the mitochondrial cofactor coenzyme Q10 and the NMDA antagonist remacemide. We found that oral administration of either coenzyme Q10 or remacemide significantly extended survival and delayed the development of motor deficits, weight loss, cerebral atrophy, and neuronal intranuclear inclusions in the R6/2 transgenic mouse model of HD. The combined treatment, using coenzyme Q10 and remacemide together, was more efficacious than either compound alone, resulting in an approximately 32 and 17% increase in survival in the R6/2 and N171-82Q mice, respectively. Magnetic resonance imaging showed that combined treatment significantly attenuated ventricular enlargement in vivo. These studies further implicate defective energy metabolism and excitotoxicity in the R6/2 and N171-82Q transgenic mouse models of HD and are of interest in comparison with the outcome of a recent clinical trial examining coenzyme Q10 and remacemide in HD patients.

Topics: Acetamides; Administration, Oral; Animals; Behavior, Animal; Body Weight; Brain; Cerebral Ventricles; Coenzymes; Disease Models, Animal; Disease Progression; Drug Evaluation, Preclinical; Drug Synergism; Female; Humans; Huntingtin Protein; Huntington Disease; Magnetic Resonance Imaging; Male; Mice; Mice, Transgenic; Motor Activity; Nerve Tissue Proteins; Nuclear Proteins; Organ Size; Survival Rate; Treatment Outcome; Ubiquinone

Oxidative modification of lipoproteins may trigger and maintain atherogenesis. We compared the effects of different antioxidants (alpha-tocopherol, probucol, ubiquinone-10) at doses similar to those used in humans in Watanabe Heritable Hyperlipidemic (WHHL) rabbits for 12 months. Aortic lesions were analyzed for their extent and cellular composition of lesions, mean thickness of fibrous caps and density of smooth muscle cells therein, content of antioxidants, non-oxidized and oxidized lipids. Compared to controls, probucol significantly lowered the extent and macrophage content of lesions and increased the existence and smooth muscle cell density of fibrous caps. alpha-Tocopherol supplementation increased the aortic content of vitamin E, but had no decreasing effect on either the accumulation of macrophage-specific antigen in the aorta or lesion size. Nevertheless, both probucol and alpha-tocopherol significantly decreased in vitro LDL oxidizability, measured under typically strong oxidative conditions. Ubiquinone-10 supplement increased lesion size and the fraction of lesions containing fibrous caps; however, LDL oxidizability remained unaffected by ubiquinone-10 treatment. None of the antioxidants tested lowered oxidized lipids within aortic tissue; however, long-term treatment with probucol provided the most effective anti-atherosclerotic effect, while alpha-tocopherol may be pro-atherogenic and ubiquinone-10 exerts ambivalent effects. Our data suggest that (i) widely used oxidation measures, such as ex-vivo LDL oxidizability, do not reflect the degree of atherosclerosis; and (ii) long-term beneficial effects of relatively low doses of antioxidants may be outweighed by high levels of plasma cholesterol in WHHL rabbits.

Topics: alpha-Tocopherol; Animals; Antioxidants; Aorta; Arteriosclerosis; Coenzymes; Disease Models, Animal; Female; Humans; Lipids; Lipoproteins, LDL; Male; Probucol; Rabbits; Ubiquinone; Vitamin E

Intimal oxidation of LDL is considered an important early event in atherogenesis, and certain antioxidants are antiatherogenic. Dietary coenrichment with vitamin E (VitE) plus ubiquinone-10 (CoQ(10), which is reduced during intestinal uptake to the antioxidant ubiquinol-10, CoQ(10)H(2)) protects, whereas enrichment with VitE alone can increase oxidizability of LDL lipid against ex vivo oxidation. In the present study, we tested whether VitE plus CoQ(10) cosupplementation is more antiatherogenic than either antioxidant alone, by use of apolipoprotein E-deficient (apoE-/-) mice fed a high-fat diet without (control) or with 0.2% (wt/wt) VitE, 0.5% CoQ(10), or 0.2% VitE plus 0.5% CoQ(10) (VitE+CoQ(10)) for 24 weeks. None of the supplements affected plasma cholesterol concentrations, whereas in the VitE and CoQ(10) groups, plasma level of the respective supplement increased. Compared with control, plasma from CoQ(10) or VitE+CoQ(10) but not VitE-supplemented animals was more resistant to ex vivo lipid peroxidation induced by peroxyl radicals. VitE supplementation increased VitE levels in aorta, heart, brain, and skeletal muscle, whereas CoQ(10) supplementation increased CoQ(10) only in plasma and aorta and lowered tissue VITE: All treatments significantly lowered aortic cholesterol compared with control, but only VitE+CoQ(10) supplementation significantly decreased tissue lipid hydroperoxides when expressed per parent lipid. In contrast, none of the treatments affected aortic ratios of 7-ketocholesterol to cholesterol. Compared with controls, VitE+CoQ(10) supplementation decreased atherosclerosis at the aortic root and arch and descending thoracic aorta to an extent that increased with increasing distance from the aortic root. CoQ(10) significantly inhibited atherosclerosis at aortic root and arch, whereas VitE decreased disease at aortic root only. Thus, in apoE-/- mice, VitE+CoQ(10) supplements are more antiatherogenic than CoQ(10) or VitE supplements alone and disease inhibition is associated with a decrease in aortic lipid hydroperoxides but not 7-ketocholesterol.

Topics: Animals; Antioxidants; Aorta; Aortic Diseases; Apolipoproteins E; Arteriosclerosis; Cholesterol, VLDL; Coenzymes; Dietary Fats; Disease Models, Animal; Lipids; Mice; Mice, Inbred C57BL; Mice, Knockout; Ubiquinone; Vitamin E

Because diabetes mellitus is associated with impairment of testicular function, ultimately leading to reduced fertility, this study was conducted to evaluate the existence of a cause-effect relationship between increased oxidative stress in diabetes and reduced mitochondrial antioxidant capacity. The susceptibility to oxidative stress and antioxidant capacity (in terms of glutathione, coenzyme Q, and vitamin E content) of testis mitochondrial preparations isolated from Goto-Kakizaki (GK) non-insulin-dependent diabetic rats and from Wistar control rats, 1 yr of age, was evaluated. It was found that GK mitochondrial preparations showed a lower susceptibility to lipid peroxidation induced by ADP/Fe(2+), as evaluated by oxygen consumption and reactive oxygen species generation. The decreased susceptibility to oxidative stress in diabetic rats was associated with an increase in mitochondrial glutathione and coenzyme Q9 contents, whereas vitamin E was not changed. These results demonstrate a higher antioxidant capacity in diabetic GK rats. We suggest this is an adaptive response of testis mitochondria to the increased oxidative damage in diabetes mellitus.

Topics: Animals; Antioxidants; Coenzymes; Diabetes Mellitus, Type 2; Disease Models, Animal; Glutathione; Glutathione Disulfide; Male; Mitochondria; Oxidative Stress; Oxygen Consumption; Rats; Rats, Inbred Strains; Rats, Wistar; Reactive Oxygen Species; Testis; Ubiquinone; Vitamin E

Coenzyme Q10 (CoQ10) is essential for ATP generation and has antioxidant properties. Decreased CoQ10 levels have been reported in human heart failure (CHF), but it remains unclear if this is a conserved feature of CHF. The objective of the study was to determine if tachycardia-induced CHF in the dog is associated with reduced CoQ10 levels. Furthermore, it was hypothesized that CoQ10 supplementation may improve CHF severity by preventing CoQ10 deficiency (if present) or via antioxidant effects.. Serum and myocardial levels of CoQ10 were examined in normal dogs (n = 6), dogs with CHF (control, n = 5), and dogs with CHF treated with CoQ10 (CoQ10; 10 mg/kg/day, n = 5). Serum CoQ10 levels did not change with CHF in control dogs, and myocardial levels were similar to those of normal dogs. CoQ10 therapy increased serum but not myocardial levels of CoQ10. In early CHF, CoQ10-treated dogs had lower filling pressures, and, in severe CHF, CoQ10-treated dogs had less hypertrophy as compared with untreated dogs. Other indices of CHF severity were similar in control and CoQ10-treated dogs.. These data indicate that CoQ10 deficiency is not present in this model of CHF. Although dramatic effects on hemodynamics were not observed, CoQ10 supplementation did appear to attenuate the hypertrophic response associated with CHF. Key words: enzymes, cardiomyopathy, hormones, antioxidant.

Topics: Animals; Antioxidants; Coenzymes; Disease Models, Animal; Dogs; Heart Failure; Hypertrophy; Male; Myocardium; Tachycardia; Ubiquinone

The aim of the work was to evaluate an influence of CoQ(10) on lactate acidosis, adenosine-5'-triphosphate (ATP) concentrations, oxidized to reduced glutathione ratio and on superoxide dismutase activity in endothelin model of cerebral ischemia in the rat. Light microscopic studies in the central nervous system and morphometric analysis of pyramidal cells in the hippocampus were also performed. Endothelins (ET-1 or ET-3; 20 pmoles) were injected into the right lateral cerebral ventricle (intracerebroventricularly). CoQ(10) was given intraperitoneally (i.p.) just before the operation (i.p. 10 mgkg b. wt.). More severe changes of investigated biochemical parameters were observed in the animals treated with ET-1 in comparison with ET-3. Recovery was noted earlier in the group subjected to ET-3 and CoQ(10) administration, than in the animals subjected to ET-1 and CoQ(10) treatment. Histopathological observations showed sparse foci of a neuronal loss in the cerebral cortex and in the hippocampus only in the ET-1 model of ischemia. Additionally more numerous dark neurons were present in above brain structures following ET-1 administration comparing with ET-3 one. Morphometrical studies demonstrated that CoQ(10) diminished neuronal injury in the hippocampal CA1, CA2 and CA3 zones. Above data indicate on neuroprotective effect of CoQ(10) as a potent antioxidant and oxygen derived free radicals scavenger in the cerebral ischemia.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Ischemia; Brain Stem; Cerebellum; Cerebral Cortex; Cerebral Ventricles; Coenzymes; Disease Models, Animal; Endothelin-1; Functional Laterality; Glutathione; Glutathione Disulfide; Hippocampus; Injections, Intraventricular; Lactates; Male; Neurons; Pyramidal Cells; Rats; Rats, Wistar; Superoxide Dismutase; Ubiquinone

The aim of the work was to evaluate the influence of CoQ10 on superoxide dismutase (SOD) activity levels in the rat model of cerebral ischemia induced by endothelins (ET-1 or ET-3). ETs (20 pmol) were injected into the right lateral cerebral ventricle and immediately CoQ10 was given intraperitoneally (10 mg/kg b.w.). In the brains of experimental animals subjected both to ET-1 and ET-2 administration there was observed a decrease of SOD activity in the brain stem, in the cerebrallum and in the cerebral cortex at all time intervals. ET-1, as compared to ET-3 evoked longer lasting disturbances in SOD activity. In the cerebellum and in the cerebral cortex positive effect of CoQ10 and recovery to the control values was noted after 4 hours in the group subjected to ET-3 injection and after 24 hours in the ET-1 treated animal. Investigated brain areas showed different sensitivity to ETs. Above data may indicate on beneficial effect CoQ10 in the cerebral ischemia via decrease of free radicals concentration.

Topics: Animals; Brain Ischemia; Brain Stem; Cerebellum; Cerebral Cortex; Coenzymes; Disease Models, Animal; Endothelin-1; Endothelin-3; Male; Rats; Rats, Wistar; Superoxide Dismutase; Ubiquinone

Coenzyme Q10 has been found to enhance recovery of function after reperfusion in numerous experimental acute ischemia-reperfusion models. We assessed whether coenzyme Q10, administered intravenously either during or 1 h before ischemia, can limit infarct size in the rabbit.. Anesthetized open-chest rabbits were subjected to 30 min of coronary artery occlusion and 4 h of reperfusion. In Protocol 1, 12 min after beginning of ischemia rabbits were randomized to intravenous infusion of 30 mg coenzyme Q10 (Eisai Co., Japan) (n = 10) or vehicle (n = 10). In Protocol 2, rabbits were randomized to 30 mg coenzyme Q10 (n = 6) or vehicle (n = 6) treatment 60 min before ischemia. Ischemic zone at risk (IZ) was assessed by blue dye and necrotic zone (NZ) by tetrazolium staining.. In both protocols, coenzyme Q10 did not alter heart rate, mean blood pressure, or regional myocardial blood flows in either the ischemic or non-ischemic zones during ischemia or reperfusion. No difference was found in IZ (as fraction of LV weight) (Protocol 1: 0.24 +/- 0.02 vs. 0.25 +/- 0.02; Protocol 2: 0.28 +/- 0.02 vs. 0.28 +/- 0.03, in the control vs. coenzyme Q10 groups, respectively). The NZ/IZ ratio was comparable between the groups in both protocols (Protocol 1: 0.22 +/- 0.04 vs. 0.26 +/- 0.04; Protocol 2: 0.21 +/- 0.06 vs. 0.30 +/- 0.06, in the control vs. coenzyme Q10 groups, respectively).. Coenzyme Q10, administered acutely either during or 60 min before myocardial ischemia, does not attenuate infarct size in the rabbit.

Topics: Animals; Coenzymes; Disease Models, Animal; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Rabbits; Random Allocation; Ubiquinone

The effect of coenzyme Q10 (CoQ10) on hepatocyte injury during endotoxin (ET) shock in rats was studied with special reference to the role of polymorphonuclear neutrophils (PMN). ET shock was induced by intravenous administration of 5 mg/kg ET, and CoQ10 was given at 20 mg/kg once or 3 times orally or intravenously. We examined plasma glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and glutamate dehydrogenase (GLDH) levels, superoxide production by PMN, the phagocytic activity of PMN, the cytotoxicity of PMN to liver cells, and histological changes in the liver. The CoQ10-treated rats showed lower levels of GOT, GPT, and GLDH than rats treated with ET only. When compared to the group given ET only superoxide production by PMN induced by 2-methyl-6-phenyl-3,7-dihydroimidazol [1,2-alpha]pyrazin-3-one (MCLA) was significantly inhibited in the group given CoQ10 intravenously and 3 times orally, but there was no significant difference in the group given CoQ10 once orally. However, the level of superoxide production by PMN stimulated by phorbol myristate acetate (PMA) was lower in all CoQ10-treated rats than in those given ET only. There was no difference in either peripheral PMN counts or PMN phagocytes between the CoQ10-treated group and the group given ET only. Histologically, the hepatocyte injury in all groups that received CoQ10 was milder than that in the ET-only group. No hepatocyte cytotoxicity by PMN was observed in any group that received CoQ10. These results suggest that both intravenous and oral administration of CoQ10 can modulate the endotoxin-activated PMN, and is useful for preventing hepatocyte injury during ET shock.

Topics: Animals; Coenzymes; Disease Models, Animal; Liver Diseases; Male; Neutrophils; Phagocytosis; Rats; Rats, Wistar; Shock, Septic; Superoxides; Ubiquinone

Glucose and steroids have been used in the treatment of children with Reye's syndrome, while carnitine and coenzyme Q10 have been the subject of some recent studies which suggest that these agents may have a role in the treatment of Reye's syndrome and Reye-like syndrome due to margosa oil poisoning. Because of the paucity of causes of Reye's syndrome seen at any one centre, the clinical variability of the disease, and limited knowledge of definite aetiologic factors, controlled clinical trials are not easy to carry out or to interpret in human cases. These caveats were overcome by evaluation of these four treatment modalities in an established margosa-oil-induced animal model of Reye's syndrome. Effectiveness of the treatment modalities was determined from clinical response and histopathologic parameters (grading of light microscopic fatty changes and ultrastructural changes in the hepatocytes). Results show that carnitine per se produces a small improvement in survival, but statistically, more significant benefit is seen with glucose administration. Carnitine plus 10% dextrose appears to produce better results. Evaluation of coenzyme Q10 and carnitine on histopathologic parameters in the liver after a sublethal dose of margosa oil showed no obvious ameliorating effect on liver pathology. Steroids (dexamethasone/methylprednisolone) had no beneficial effects in reducing mortality, affecting glycogen storage or lipid accumulation. Changes in the mitochondria, ribosomes and endoplasmic reticulum were unaltered from the groups treated with margosa oil alone. While glucose and carnitine supplements appear to be beneficial, the other modes of therapy do not seem to hold much promise in the treatment of Reye-like syndrome in the margosa-oil-induced animal model.

Topics: Animals; Carnitine; Coenzymes; Dexamethasone; Disease Models, Animal; Female; Glucose; Glycerides; Methylprednisolone; Mice; Mice, Inbred ICR; Plant Oils; Reye Syndrome; Steroids; Terpenes; Ubiquinone

We studied the effects of coenzyme Q10 (CoQ10) on pulmonary function and chemical mediators in a canine model of hemorrhagic shock. One group received 10 mg/kg of CoQ10 before hemorrhage. During the study, percent change from baseline of peak airway pressure, total lung compliance of the lung and chest wall, and blood lactate levels appeared to be significantly smaller in dogs pretreated with CoQ10 than in controls. Furthermore, CoQ10 was found to maintain blood histamine levels and to attenuate the increase in leukotriene C4. The mechanism of the beneficial effects of CoQ10 in hemorrhagic shock is presently unknown, but our data suggest that it may be useful in the treatment of hemorrhagic shock.

Topics: Airway Resistance; Animals; Blood Gas Analysis; Coenzymes; Disease Models, Animal; Dogs; Hemodynamics; Histamine; Lactates; Lung Compliance; Pulmonary Ventilation; Shock, Hemorrhagic; SRS-A; Ubiquinone

Ischemic insult has been considered a cause of cellular injuries under certain circumstance, such as the disturbance of energy metabolism, the alternation of calcium homeostasis, the production of oxygen radical and the release of lysosomal protease. The present study was designed to clarify the pathophysiological effects of coenzyme Q10 (CoQ10), diltiazem, superoxide dismutase (SOD) and urinastatin on the development and progression of ischemic acute renal failure (IARF) of the rat. At 24 hours after reflow following 45 minutes ischemia, serum urea nitrogen, creatinine and fractional excretion of sodium were 99.3 mg/dl, 3.14 mg/dl, 5.95% respectively, in non-treated IARF rats. Renal ATP content was reduced to 0.91 micrograms/mg. prot. from 10.59 micrograms/mg. prot. at 10 minutes after ischemic insult, and remained at almost the same level throughout the entire 45 minutes ischemia. Although the subsequent blood reflow resulted in the recovery of ATP content, it was up to 50% of normal level at 24 hours after reflow following 45 minutes ischemia. During the ischemic period, the pathological changes were mild, whereas, after reflow, tissue involvement was mainly localized in the S3 segment of the proximal tubule. Major alteration were the loss of brush border, high amplitude swelling of mitochondria with matrical densities and fragmentation of the epithelial cell. At 24 hours after reflow, it was observed that renal function was superior in IARF rats treated with CoQ10, diltiazem, SOD and urinastatin. The treated rats also had higher ATP contents and showed less pathological changes than non-treated rats. Among these inhibitory agents, diltiazem exerted the most reliable effect. From these results, it was concluded that IARF was obviously caused by such pathophysiological mechanisms as mentioned above. Especially, Ca influx into the cells is one of the most important factors on pathogenesis of IARF.

Topics: Acute Kidney Injury; Adenosine Triphosphate; Animals; Calcium; Coenzymes; Diltiazem; Disease Models, Animal; Glycoproteins; Kidney; Male; Rats; Rats, Inbred Strains; Superoxide Dismutase; Trypsin Inhibitors; Ubiquinone

This study was undertaken to determine whether pretreatment of the donor rat with coenzyme Q10 (CoQ10) would protect against hepatic ischemia induced for 30 minutes at normothermic body temperature. Fresh liver transplants were used as controls (minus warm ischemia of 30 minutes) and gave a 1-week survival rate of 84.6%. CoQ10 was administered intravenously (10 mg/kg body weight) to the donor rat 1 hour before induction of warm ischemia (group A). In another group (B), the same dose was given intravenously not only to the donor rat but also to the recipient rat 1 hour before grafting. None of the placebo group survived more than 2 days. The 1-week survival rates of the groups pretreated with CoQ10 were 45.5% for group A and 50% for group B. There was no significant difference between groups A and B. A statistically significant difference was demonstrated between the placebo group and both CoQ10-treated groups (p less than 0.05). It was therefore assumed that CoQ10, accumulated in the donor liver, was a primary factor in improving survival. Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphatase (SALP), total bilirubin, and total protein were measured by means of light and electron microscopic examination of the liver 6 months after transplantation. Long-term-surviving rats with transplanted, ischemically damaged liver that was pretreated with CoQ10 showed a decrease in the activity of SGOT and SGPT and an increase in levels of total protein to the normal range (as well as to those levels exhibited by fresh-liver-transplanted rats) with practically no change in levels of SALP, total bilirubin, or in histologic findings. These results indicate that donor pretreatment with CoQ10 is useful for increasing survival after warm ischemic damage of rat liver grafts.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Bilirubin; Coenzymes; Disease Models, Animal; Ischemia; Liver; Liver Transplantation; Male; Mortality; Rats; Rats, Inbred Strains; Ubiquinone