Effect of melatonin on motor performance and brain cortex mitochondrial function during ethanol hangover.
Increased reactive oxygen species generation and mitochondrial dysfunction occur during ethanol hangover. The aim of this work was to study the effect of melatonin pretreatment on motor performance and mitochondrial function during ethanol hangover. Male mice received melatonin solution or its vehicle in drinking water during 7 days and i.p. injection with EtOH (3.8 g/kg BW) or saline at the eighth day. Motor performance and mitochondrial function were evaluated at the onset of hangover (6h after injection). Melatonin improved motor coordination in ethanol hangover mice. Malate-glutamate-dependent oxygen uptake was decreased by ethanol hangover treatment and partially prevented by melatonin pretreatment. Melatonin alone induced a decrease of 30% in state 4 succinate-dependent respiratory rate. Also, the activity of the respiratory complexes was decreased in melatonin-pretreated ethanol hangover group. Melatonin pretreatment before the hangover prevented mitochondrial membrane potential collapse and induced a 79% decrement of hydrogen peroxide production as compared with ethanol hangover group. Ethanol hangover induced a 25% decrease in NO production. Melatonin alone and as a pretreatment before ethanol hangover significantly increased NO production by nNOS and iNOS as compared with control groups. No differences were observed in nNOS protein expression, while iNOS expression was increased in the melatonin group. Increased NO production by melatonin could be involved in the decrease of succinate-dependent oxygen consumption and the inhibition of complex IV observed in our study. Melatonin seems to act as an antioxidant agent in the ethanol hangover condition but also exhibited some dual effects related to NO metabolism.
Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
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Karadayian
Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
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Bustamante
Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
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Czerniczyniec
Laboratorio de Neurobiología y Ritmos, Facultad de Medicina, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
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Cutrera
Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina. Electronic address: slarnaiz@ffyb.uba.ar.
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Lores-Arnaiz
D019973:Alcohol-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000009:adverse effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D000431:Ethanol / Q000009:adverse effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism
D000975:Antioxidants; D002492:Central Nervous System Depressants; D009589:Nitrogen Oxides; D000431:Ethanol; D006861:Hydrogen Peroxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; D008550:Melatonin; D010100:Oxygen
ethanol hangover; melatonin; mitochondrial function; mitochondrial membrane potential; motor coordination; oxidative stress