coenzyme-q10 and Nerve-Degeneration

Coenzyme Q

Topics: Adult; Aged; Ataxia; Calcium-Binding Proteins; Cell Adhesion Molecules, Neuronal; Collectins; Cross-Sectional Studies; Female; Genetic Loci; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Mitochondrial Diseases; Muscle Weakness; Nerve Degeneration; Nerve Tissue Proteins; Neural Cell Adhesion Molecules; Neurons; Polymorphism, Single Nucleotide; Receptors, Scavenger; Ubiquinone

An open-label dose-escalation trial was performed to assess the safety and tolerability of high doses of coenzyme Q10 (CoQ10) in ALS. CoQ10, a cofactor in mitochondrial electron transfer, may improve the mitochondrial dysfunction in ALS. In this study, CoQ10 was safe and well tolerated in 31 subjects treated with doses as high as 3,000 mg/day for 8 months.

Topics: Amyotrophic Lateral Sclerosis; Central Nervous System; Coenzymes; Dose-Response Relationship, Drug; Drug Tolerance; Energy Metabolism; Female; Free Radical Scavengers; Humans; Male; Maximum Tolerated Dose; Middle Aged; Mitochondria; Nerve Degeneration; Neurons; Neuroprotective Agents; 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 neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which produces Parkinsonism, is mediated by its metabolite 1-methyl-4-phenylpyridinium ion (MPP+). When injected into the striatum MPP+ is accumulated by dopaminergic nerve terminals and is then retrogradely transported to the substantia nigra compacta. The mechanism by which it mediates cell death involves both inhibition of complex I of the electron transport chain and free radical generation. In the present experiments we found that administration of the free radical spin trap N-tert-butyl-alpha-(2-sulfophenyl) nitrone (S-PBN) significantly attenuated substantia nigra cell loss produced by MPP+ administration into rat striatum. We also found that coadministration of coenzyme Q10 with nicotinamide, which attenuates energy depletion, significantly blocked MPP(+)-induced substantia nigra damage. Last, we found that a single administration of MPP+ into rat striatum can produce progressive cell loss in the substantia nigra and that administration of S-PBN starting 7 days after administration of MPP+ can block the ensuing neuronal damage. These observations suggest that a one-time exposure to a neurotoxic agent may result in progressive neuronal degeneration mediated by oxidative stress.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Coenzymes; Cyclic N-Oxides; Dopamine Agents; Drug Combinations; Ions; Male; Nerve Degeneration; Niacinamide; Nitrogen Oxides; Oxidative Stress; Rats; Rats, Sprague-Dawley; Spin Labels; Substantia Nigra; Time Factors; Ubiquinone