coenzyme-q10 and 4-hydroxy-2-nonenal

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

Deficiency of energy supply is a major complication contributing to the syndrome of heart failure (HF). Because the concurrent activity profile of mitochondrial bioenergetic enzymes has not been studied collectively in human HF, our aim was to examine the mitochondrial enzyme defects in left ventricular myocardium obtained from explanted end-stage failing hearts. Compared with nonfailing donor hearts, activity rates of complexes I and IV and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase, and aconitase were lower in HF, as determined spectrophotometrically. However, activity rates of complexes II and III and citrate synthase did not differ significantly between the two groups. Protein expression, determined by Western blotting, did not differ between the groups, implying posttranslational perturbation. In the face of diminished total glutathione and coenzyme Q10 levels, oxidative modification was explored as an underlying cause of enzyme dysfunction. Of the three oxidative modifications measured, protein carbonylation was increased significantly by 31% in HF (P < 0.01; n = 18), whereas levels of 4-hydroxynonenal and protein nitration, although elevated, did not differ. Isolation of complexes I and IV and F1FoATP synthase by immunocapture revealed that proteins containing iron-sulphur or heme redox centers were targets of oxidative modification. Energy deficiency in end-stage failing human left ventricle involves impaired activity of key electron transport chain and Krebs cycle enzymes without altered expression of protein levels. Augmented oxidative modification of crucial enzyme subunit structures implicates dysfunction due to diminished capacity for management of mitochondrial reactive oxygen species, thus contributing further to reduced bioenergetics in human HF.

Topics: Aconitate Hydratase; Aldehydes; Blotting, Western; Citrate (si)-Synthase; Citric Acid Cycle; Electron Transport Chain Complex Proteins; Electron Transport Complex I; Electron Transport Complex IV; Female; Glutathione; Heart Failure; Heart Ventricles; Humans; Isocitrate Dehydrogenase; Ketoglutarate Dehydrogenase Complex; Malate Dehydrogenase; Male; Middle Aged; Mitochondria, Heart; Mitochondrial Proton-Translocating ATPases; Myocardium; Oxidative Phosphorylation; Protein Carbonylation; Protein Processing, Post-Translational; Reactive Oxygen Species; Ubiquinone

It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10) is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group). In the neomycin group, utricles were cultured with neomycin (1 mM) to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM). Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

Topics: Aldehydes; Animals; Anti-Bacterial Agents; Calmodulin; Cell Count; Cell Death; Cell Survival; Hair Cells, Vestibular; Male; Mice; Mice, Inbred CBA; Neomycin; Protective Agents; Reactive Oxygen Species; Saccule and Utricle; Ubiquinone

To investigate the neuroprotective effects of coenzyme Q10 and/or a vitamin E analogue on retinal damage both in vitro and in vivo.. We employed cultured retinal ganglion cells (RGC-5, a rat ganglion cell-line transformed using E1A virus) in vitro. Cell damage was induced by 24-h hydrogen peroxide (H2O2) exposure, and cell viability was measured using tetrazolium salt (WST-8). To examine the retinal damage induced by intravitreal N-methyl-d-aspartate (NMDA) injection in mice in vivo, coenzyme Q10 at 10 mg/kg with or without alpha-tocopherol at 10 mg/kg was administered orally (p.o.) each day for 14 days, with NMDA being intravitreally injected on day 7 of this course.. In RGC-5, a combination of coenzyme Q10 and trolox, a water-soluble vitamin E analogue (a derivative of alpha-tocopherol), prevented cell damage more effectively than either agent alone. Coenzyme Q10 and alpha-tocopherol (separately or together) reduced the retinal damage, number of TUNEL-positive cells in the ganglion cell layer (GCL), and 4-hydroxyl-2-nonenal (4-HNE) expression induced by NMDA in mice in vivo.. Coenzyme Q10 and/or these vitamin E analogues exert neuroprotective effects against retinal damage both in vitro and in vivo.

Topics: Aldehydes; Animals; Antioxidants; Apoptosis; Cell Line, Transformed; Chromans; Drug Administration Routes; Drug Interactions; Excitatory Amino Acid Agonists; Hydrogen Peroxide; In Situ Nick-End Labeling; Mice; N-Methylaspartate; Oxidants; Oxidative Stress; Rats; Retina; Retinal Ganglion Cells; Ubiquinone; Vitamin E; Vitamins

The results of this study indicate that coenzyme Q10 reduces cochlear oxidative stress induced by acoustic overstimulation.. We investigated the effects of coenzyme Q10 on noise-induced hearing loss in guinea pigs.. Animals received water-soluble coenzyme Q10 intraperitoneally 2 h before noise exposure. Seven days after noise exposure (130 dB sound pressure level for 3 h), the auditory brainstem response (ABR) threshold shift and cochlear hair cell damage were assessed.. We observed that the ABR threshold shift was significantly less in the coenzyme Q10 group than in the vehicle control group. In addition, the percentage of missing outer hair cells was lower in the coenzyme Q10 group than in the control group. Moreover, 2 days after administration of coenzyme Q10, increased antioxidative activity in the cochlea, as measured by analysis of hydroxy radical scavenging activity by electron spin resonance was observed.

Topics: Aldehydes; Animals; Antioxidants; Auditory Threshold; Electron Spin Resonance Spectroscopy; Evoked Potentials, Auditory, Brain Stem; Free Radical Scavengers; Guinea Pigs; Hair Cells, Auditory, Outer; Hearing Loss, Noise-Induced; Hydroxyl Radical; Immunohistochemistry; Male; Ubiquinone

Recently some reports about the oxidative stress in renal transplant recipients have been published. The role of coenzyme Q10 (CoQ10) as radical scavanger is largely known. The aim of our study was to evaluate the protective role of CoQ10 in renal transplant recipients on lipid peroxidation and lipids parameters, as well as its influence on antioxidant enzymes, neutrophils chemiluminescence and urinary enzymes. The study was performed in 11 long term allograft recipients treated additionally with CoQ10 90 mg/day in three doses, 30 mg each for four weeks. The malonyldialdehyde (MDA) and 4-hydroxynonenal (4-HNE), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the basic parameters of lipid metabolism such as total cholesterol (TC), high and low density lipoproteins (HDL, LDL), triglycerides (TG), atherogenicity indicators [LDL/HDL; (TC-HDL)/HDL] were evaluated. The chemiluminescence of neutrophils (luminol, fLMP-method) were mesured and the activity of N-acetyl-beta-D-glucosaminidase (NAG), alanylaminopeptidase (AAP), elastase, alpha-1-antitrypsin. All parameters were estimated before and after CoQ10 treatment. Statistically significant changes were noticed with the LDL and atherogenicity indicators (p < 0.01) (decrease) as well as HDL level (p < 0.001) (increase). Also the significant decrease of fMLP stimulated PMNL chemiluminescence (p < 0.05) confirms the antioxidative properties of CoQ10. The significant increase of NAG activity (p < 0.05) can't be the result of nephrotoxic effect, because NAG-B is unchanged. Serum concentration of creatinine and cyclosporine A in renal allograft recipients was unchanged after CoQ10 treatment. The presented date shows that further study with CoQ10 treatment in renal transplant in larger numbers and over longer periods should be considered.

Topics: Acetylglucosaminidase; Adult; Aldehydes; alpha 1-Antitrypsin; CD13 Antigens; Coenzymes; Female; Free Radical Scavengers; Glutathione Peroxidase; Humans; Kidney Transplantation; Lipid Peroxidation; Lipids; Luminescent Measurements; Male; Malondialdehyde; Neutrophils; Oxidative Stress; Pancreatic Elastase; Superoxide Dismutase; Ubiquinone