ubiquinone and Necrosis

Sepsis is one of the main causes of death among critically ill patients. Sepsis pathogenesis includes infection by gram-negative and gram-positive bacteria, fungi, or both; exacerbated inflammatory response; hypotension, with potential to cause vasodilatory shock; and lesser delivery of oxygen to tissues due to impairment of oxygen utilization by cells. The participation of reactive species and/or free radicals such as nitric oxide (NO), peroxynitrite (ONOO

Topics: Adenosine Triphosphate; Animals; Antioxidants; Apoptosis; Humans; Melatonin; Mitochondria; Multiple Organ Failure; Necrosis; NF-kappa B; Organophosphorus Compounds; Oxidative Stress; Selenium; Sepsis; Ubiquinone; Vitamins

Coenzyme Q10 (CoQ10) which acts as an electron transporter in the mitochondrial respiratory chain has many beneficial effects on liver diseases. In our previous research, CoQ10 has been found to attenuate acetaminophen (APAP)-induced acute liver injury (ALI). However, whether CoQ10 administration is still effective at the late stage of APAP overdose is still unknown. In this study, we aimed to test CoQ10 efficacy at the late stage of APAP overdose. C57BL/6J mice were intraperitoneally treated with APAP to induce liver injury. CoQ10 (5 mg/kg) was given to mice at 16 h after APAP treatment. The results showed that while CoQ10 treatment at 16 h post-APAP overdose had no effects on the expression of ROS generated genes or scavenged genes, it still significantly decreased necrosis of hepatocytes following APAP-induced ALI. Moreover, CoQ10 increased MerTK+ macrophages accumulation in the APAP-overdose liver and inhibition of MerTK signaling partly abrogated the protective role of CoQ10 treatment on the hepatic necrosis. CoQ10 treatment also significantly enhanced hepatocytes proliferation as shown in the increased 5-bromodeoxyuridine incorporation in the APAP-intoxicated mice liver section. In addition, CoQ10 treatment increased hepatic Proliferating Cell Nuclear Antigen (PCNA) and Cyclin D1 expression and promoted activation of the β-catenin signaling in APAP-overdose mice. To conclude, these data provide evidence that CoQ10 treatment is still effective at the late stage of APAP-induced ALI and promotes resolution of necrosis and liver regeneration following ALI.

Topics: Acetaminophen; Animals; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Hepatocytes; Liver; Liver Regeneration; Mice; Mice, Inbred C57BL; Necrosis; Ubiquinone

2,3-Dimethoxy-5-methyl-p-benzoquinone is a common chemical structure of coenzyme Q (CoQ) that conjugates different lengths of an isoprenoid side chain at the 6-position of the p-benzoquinone ring. In a series of studies to explore the cytotoxic mechanism of CoQ homologues with a short isoprenoid side chain, we found that a CoQ analogue without an isoprenoid side chain, CoQ

Topics: Adenosine Triphosphate; Benzoquinones; Carbohydrate Metabolism; Cell Death; Cell Survival; HeLa Cells; Humans; Necrosis; Oxidative Stress; Structure-Activity Relationship; Sulfhydryl Compounds; Terpenes; Ubiquinone

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

Although oxidative stress has been strongly implicated in the development of acute pancreatitis (AP), antioxidant therapy in patients has so far been discouraging. The aim of this study was to assess potential protective effects of a mitochondria-targeted antioxidant, MitoQ, in experimental AP using in vitro and in vivo approaches. MitoQ blocked H2O2-induced intracellular ROS responses in murine pancreatic acinar cells, an action not shared by the control analogue dTPP. MitoQ did not reduce mitochondrial depolarisation induced by either cholecystokinin (CCK) or bile acid TLCS, and at 10 µM caused depolarisation per se. Both MitoQ and dTPP increased basal and CCK-induced cell death in a plate-reader assay. In a TLCS-induced AP model MitoQ treatment was not protective. In AP induced by caerulein hyperstimulation (CER-AP), MitoQ exerted mixed effects. Thus, partial amelioration of histopathology scores was observed, actions shared by dTPP, but without reduction of the biochemical markers pancreatic trypsin or serum amylase. Interestingly, lung myeloperoxidase and interleukin-6 were concurrently increased by MitoQ in CER-AP. MitoQ caused biphasic effects on ROS production in isolated polymorphonuclear leukocytes, inhibiting an acute increase but elevating later levels. Our results suggest that MitoQ would be inappropriate for AP therapy, consistent with prior antioxidant evaluations in this disease.

Topics: Acinar Cells; Acute Disease; Animals; Antioxidants; Apoptosis; Ceruletide; Cholecystokinin; Disease Models, Animal; Inflammation; Male; Membrane Potential, Mitochondrial; Mice; Mitochondria; Necrosis; Organophosphorus Compounds; Oxidative Stress; Pancreas; Pancreatitis; Reactive Oxygen Species; Taurolithocholic Acid; Ubiquinone

Autologous fat is an attractive soft-tissue filler in plastic and reconstructive surgery. The success of the procedure relies strongly on the technique of transferring viable preadipocytes. Among other factors, preadipocyte viability is impaired by local anesthetics. Application of coenzyme Q10 is being performed by aesthetic plastic surgeons to enhance the success of lipotransfer. The aim of this study was to evaluate the effect of Q10 on preadipocyte viability with special regard to impairment after lidocaine treatment.. Preadipocytes were pretreated with coenzyme Q10 or vehicle control followed by incubation with lidocaine for 30 min. Viability and apoptosis were assessed by FACS analysis and Western blot.. Coenzyme Q10 did not improve viability nor have any effect on investigated apoptosis parameters. Preadipocyte viability was reduced after lidocaine treatment. Surface binding of annexin V, cleavage of caspase-3, and abundance of subdiploid cells were not detectable though, suggesting that necrosis rather than apoptosis is the cause for reduced preadipocyte viability.. Our results indicate that Q10 does not improve preadipocyte viability. Preadipocyte cell death induced by lidocaine is not caused by apoptosis but by necrosis, which cannot be prevented by coenzyme Q10. These findings should be taken into account when searching for solutions to improve preadipocyte viability in the context of soft tissue engineering and autologous fat transfer.

Topics: Adipocytes; Adipose Tissue; Anesthetics, Local; Apoptosis; Cell Survival; Humans; Lidocaine; Necrosis; Transplantation, Autologous; Ubiquinone

Our current understanding of the nature of cell death that is associated with fatal organophosphate poisoning and the underlying cellular mechanisms is surprisingly limited. Taking advantage of the absence in an in vitro system of acetylcholinesterase, the pharmacological target of organophosphate compounds, the present study evaluated the hypothesis that the repertoire of cholinergic receptor-independent cellular events that underlie fatal organophosphate poisoning entails induction of mitochondrial dysfunction, followed by bioenergetic failure that leads to necrotic cell death because of ATP depletion. Pheochromocytoma PC12 cells incubated with the organophosphate pesticide mevinphos (0.4 or 4mumol) for 1 or 3h underwent a dose-related and time-dependent loss of cell viability that was not reversed by muscarinic (atropine) or nicotinic (mecamylamine) blockade. This was accompanied by depressed NADH cytochrome c reductase, succinate cytochrome c reductase or cytochrome c oxidase activity in the mitochondrial respiratory chain, reduced mitochondrial transmembrane potential, decreased ATP concentration, elevated ADP/ATP ratio, increased lactate dehydrogenase release and necrotic cell death. We conclude that Mev induces cholinergic receptor-independent necrotic cell death by depressing the activity of Complexes I to IV in the mitochondrial respiratory chain, eliciting reduction in mitochondrial transmembrane potential, depleting intracellular ATP contents and damaging cell membrane integrity.

Topics: Adenosine Triphosphate; Animals; Atropine; Chemical Warfare Agents; Cholesterol; Cholinesterase Inhibitors; Electron Transport; Electron Transport Complex IV; Energy Metabolism; Insecticides; L-Lactate Dehydrogenase; Mecamylamine; Membrane Potential, Mitochondrial; Mevinphos; Mitochondria; Muscarinic Antagonists; NADH Dehydrogenase; Necrosis; Nerve Tissue Proteins; Nicotinic Antagonists; Oxidative Phosphorylation; PC12 Cells; Polyethylene Glycols; Rats; Receptors, Cholinergic; Ubiquinone

The role of biomembranes in the chronic toxicity of environmentally occurring chromium acetate hydroxide was investigated by using primary human fibroblasts. Transport of chromium acetate hydroxide across the plasma membrane of the cell, and the effects of chromium (III) ions on the plasma membrane as well as other intracellular membranes, were determined during six weeks of continuous exposure by using atomic absorption spectrometry, observation of cell morphology, membrane integrity assays (for lactate dehydrogenase leakage and lysosomal membrane disruption), and mitochondrial assays (for mitochondrial dehydrogenase activity and mitochondrial transmembrane potential analysis). The type of cell death induced by long-term exposure was determined in terms of phosphatidylserine externalisation, caspase-3 activation, and chromatin fragmentation. Chromium acetate hydroxide, at a concentration of 100 micromol/l, accumulated in exposed cells, inflicting plasma membrane damage and suppressing mitochondrial function. Antioxidant co-enzyme Q, at a concentration of 10 micromol/l, partially prevented plasma membrane damage and mitochondrial dysfunction. Exposure to chromium acetate hydroxide produced apoptosis, necrosis and an intermediate type of cell death in primary human fibroblasts. These results show that the plasma membrane and mitochondrial membrane are important targets for chronic chromium acetate hydroxide toxicity, and that this in vitro system holds promise for studying the toxicity resulting from long-term exposure to metal ions.

Topics: Apoptosis; Cells, Cultured; Chromium Compounds; Dose-Response Relationship, Drug; Environmental Pollutants; Fibroblasts; Humans; Intracellular Membranes; L-Lactate Dehydrogenase; Lysosomes; Mitochondria; Necrosis; Organometallic Compounds; Skin; Ubiquinone

The aim of the study was to observe the effect of coenzyme Q10 and vitamin E supplementation on the course of the regeneration process of the longissimus lumborum muscle after bupivacaine-induced myonecrosis as well as to determine the correlation between the level of those substances in plasma and their levels in damaged and non-damaged muscular tissue in pigs. The obtained results indicate that the course of regeneration of a damaged muscle is affected to a higher extent by coenzyme Q10 than by vitamin E. The administration of coenzyme Q10 and vitamin E has a significant impact on the increase in the level of those substances in damaged muscles and plasma of animals.

Topics: Anesthetics, Local; Animal Feed; Animals; Antioxidants; Bupivacaine; Coenzymes; Female; Muscle, Skeletal; Muscular Diseases; Necrosis; Regeneration; Swine; Swine Diseases; Ubiquinone; Vitamin E

The aim of this study was to investigate if feeding with carbonyl iron would facilitate the development of preneoplastic lesions initiated by diethylnitrosamine (DEN) and promoted by CCl4-induced liver cirrhosis.. Male Wistar rats were fed a diet with 1.25%-2.5% carbonyl iron for 23 weeks and received intragastric injections of CCl4 (1.0 or 2.0 ml/kg per week) for 13 weeks, followed by one i.p. injection of DEN (200 mg/kg), after which CCl4 was administered for 8 additional weeks. Animals were killed 48 h after the first CCl4 injection to evaluate liver necrosis, 8 weeks later to evaluate fibrosis, and 9 weeks after DEN to determine formation of glutathione S-transferase 7,7 (GST-7,7) positive foci.. Treatment with iron counteracted the increased serum alanine aminotransferase levels and liver necrosis following CCl4 administration. Hepatic levels of reduced Q9 and alpha-tocopherol were elevated in rats treated with CCl4 and decreased in rats treated with iron compared to the controls. Fibrogenesis was not altered by iron treatment. Nine weeks after DEN initiation, the number and volume density of GST-7,7-positive foci in rats treated with CCl4 were significantly increased as compared with controls, but co-treatment with iron inhibited this increase. Apoptotic index was increased in iron-loaded livers, and labelling index (the fraction of S-phase hepatocytes) was decreased by co-treatment with iron in livers exposed to CCl4.. Carbonyl iron depleted hepatic levels of antioxidants, it decreased CCl4-induced necrosis and cell proliferation, it enhanced apoptosis and did not facilitate fibrogenesis. These effects together may explain the suppression of CCl4-induced promotion after DEN initiation exerted by carbonyl iron in the present study.

Topics: Animals; Antioxidants; Apoptosis; Body Weight; Carbon Tetrachloride; Carcinogens; Cell Division; Diet; Diethylnitrosamine; Iron; Kupffer Cells; Liver; Liver Neoplasms, Experimental; Male; Necrosis; Organ Size; Rats; Rats, Wistar; Ubiquinone; Vitamin E

A combination of electrophysiological, pathological, and biochemical studies were performed in myopathy induced by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Simvastatin (a lipophilic inhibitor) or pravastatin (a hydrophilic inhibitor) were administered by gavage to rabbits. In Group I (simvastatin-treated group, 50 mg/kg/day for 4 weeks), four rabbits showed muscle necrosis and high serum creatine kinase (CK) levels, and all six rabbits showed electrical myotonia. In Group II (pravastatin-treated group, 100 mg/kg/day for 4 weeks), no rabbit showed either condition. In Group III (pravastatin-treated group, 200 mg/kg/day for 3 weeks plus 300 mg/kg/day for 3 weeks), one rabbit showed muscle necrosis and high serum CK level and two rabbits showed electrical myotonia. The pathological findings were muscle fiber necrosis and degeneration with increased acid phosphatase activity by light microscopy, autophagic vacuoles and mitochondrial swelling, and disruption and hypercontraction of myofibrils by electron microscopy. Ubiquinone content decreased in skeletal muscle by 22 to 36% in Group I, by 18 to 52% in Group II, and by 49 to 72% in Group III. However, mitochondrial enzyme activities of respiratory chain were normal in all groups. These results indicate that myopathy was not induced by a secondary dysfunction of mitochondrial respiration due to low ubiquinone levels.

Topics: Animals; Cholesterol; Creatine Kinase; Electromyography; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Microscopy, Electron; Mitochondria, Muscle; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Myotonia; Necrosis; Phospholipids; Pravastatin; Rabbits; Simvastatin; Tissue Distribution; Ubiquinone

Cerebral ischemia followed by oxygen reperfusion induces apoptosis in hippocampal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). The overproduction of oxygen-free radicals that occurs in the tissues of SHRSP is implicated in reoxygenation injury after hypoxia. Antioxidants inhibit reoxygenation injury in hippocampal slices, and temporal cortices in Alzheimer's disease increase sensitivity to oxygen-free radicals. Because this sensitivity may contribute to the development of the disease, we have studied hypoxia and oxygen reperfusion using cortical neurons isolated from WKY and SHRSP (at 15 days of gestation). We have tried to determine whether cortical neurons are damaged under these conditions, and whether neurons from SHRSP are more vulnerable than those from WKY. We have tried also to verify whether neuronal damage is minimized by vitamin E using the following techniques: (a) Trypan blue staining, (b) in situ staining of apoptosis, (c) ultrastructural examination, and (d) measurement of lactic dehydrogenase (LDH) activity in the bathing medium. Furthermore, we have examined the mechanisms involved in the development of neuronal damage and have studied ways of minimizing it. We demonstrated that 36 hours of hypoxia significantly increased the rate of cell death in SHRSP (p < 0.01), although 12 to 24 hours of hypoxia did not increase cell death in either WKY or SHRSP. In addition, 6 to 36 hours of hypoxia and 1.5 to 5 hours of oxygen reperfusion heavily damaged cells of both WKY and SHRSP, and most became apoptotic or necrotic. In contrast, cells incubated with 50 to 300 microg/ml of vitamin E remained intact, although 10 to 20 microg/ml of vitamin E did not totally preserve the cells. Moreover, vitamin E protected the neurons from high concentrations of sodium nitroprusside (nitric oxide donor) in a dose-dependent manner. Vitamin E, when added to the cells, increased in concentration in a time-dependent manner over a 24-hour period and in a dose-dependent manner below 200 microg/ml, and it was detected mostly in the mitochondria. We also demonstrated that serial treatments with allopurinol (a xanthine oxidase inhibitor) or superoxide dismutase preserved neurons during hypoxia and oxygen reperfusion. These data indicate that SHRSP neurons are weaker than WKY neurons in long-term hypoxia; oxygen radical generation occurs in the early minutes after reperfusion, and then the oxygen-free radicals cause hea

Topics: Animals; Antioxidants; Apoptosis; Benzoquinones; Cerebral Cortex; Cerebrovascular Disorders; Free Radical Scavengers; Genetic Predisposition to Disease; Hypoxia, Brain; Necrosis; Neurons; Nitric Oxide; Osmolar Concentration; Oxygen; Rats; Rats, Inbred SHR; Rats, Wistar; Reperfusion; Superoxide Dismutase; Ubiquinone; Vitamin E

Topics: Allopurinol; Animals; Aspartate Aminotransferases; Coenzymes; Dose-Response Relationship, Drug; Free Radicals; Glutathione; Liver; Necrosis; Oxygen; Rats; Rats, Inbred Lew; Reperfusion Injury; Superoxide Dismutase; Temperature; Ubiquinone

Topics: Animals; Cardiomyopathies; Coenzymes; Female; Isoproterenol; Male; Mitochondria, Heart; Myocardium; Necrosis; Rats; Ubiquinone

Topics: Age Factors; Albumins; Animals; Body Weight; Cystine; Dietary Carbohydrates; Dietary Proteins; Liver; Liver Diseases; Liver Regeneration; Methionine; Necrosis; Selenium; Ubiquinone; Vitamins; Yeast, Dried

Topics: Anemia; Animals; Body Weight; Cathepsins; Chickens; Diet; Gizzard, Avian; Hemoglobins; Hemorrhagic Disorders; Liver; Liver Extracts; Myocardium; Necrosis; Poultry Diseases; Turkeys; Ubiquinone; Vitamin E; Vitamin E Deficiency; Yeast, Dried