CONICET | Buscador de Institutos y Recursos Humanos

Abstract?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 (6 h 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 succinatedependent 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. 2014 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: melatonin, ethanol hangover, motor coordination, mitochondrial function, mitochondrial membrane potential, oxidative stress.