Karadayian A G, Bustamante J, Czerniczyniec A, Cutrera R A, Lores-Arnaiz S
Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
Laboratorio de Neurobiología y Ritmos, Facultad de Medicina, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
Neuroscience. 2014 Jun 6;269:281-9. doi: 10.1016/j.neuroscience.2014.03.062. Epub 2014 Apr 5.
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.
乙醇宿醉期间会出现活性氧生成增加和线粒体功能障碍。本研究的目的是探讨褪黑素预处理对乙醇宿醉期间运动能力和线粒体功能的影响。雄性小鼠在7天内饮用含褪黑素溶液或其溶剂的水，并在第8天腹腔注射乙醇（3.8 g/kg体重）或生理盐水。在宿醉开始时（注射后6小时）评估运动能力和线粒体功能。褪黑素改善了乙醇宿醉小鼠的运动协调性。乙醇宿醉处理降低了苹果酸-谷氨酸依赖性氧摄取，而褪黑素预处理可部分预防这种降低。单独使用褪黑素可使状态4琥珀酸依赖性呼吸速率降低30%。此外，在褪黑素预处理的乙醇宿醉组中，呼吸复合体的活性也降低。宿醉前进行褪黑素预处理可防止线粒体膜电位崩溃，与乙醇宿醉组相比，过氧化氢生成减少79%。乙醇宿醉导致一氧化氮生成减少25%。与对照组相比，单独使用褪黑素以及在乙醇宿醉前进行预处理可显著增加nNOS和iNOS产生的一氧化氮。未观察到nNOS蛋白表达的差异，而褪黑素组中iNOS表达增加。褪黑素增加一氧化氮生成可能与本研究中观察到的琥珀酸依赖性氧消耗减少和复合体IV抑制有关。在乙醇宿醉情况下，褪黑素似乎起到抗氧化剂的作用，但也表现出一些与一氧化氮代谢相关的双重效应。
