title: Alcohol hangover induces mitochondrial dysfunction and free radical production in mouse cerebellum.
abstract: Alcohol hangover (AH) is defined as the temporary state after alcohol binge-like drinking, starting when ethanol (EtOH) is absent in plasma. Previous data indicate that AH induces mitochondrial dysfunction and free radical production in mouse brain cortex. The aim of this work was to study mitochondrial function and reactive oxygen species production in mouse cerebellum at the onset of AH. Male mice received a single i.p. injection of EtOH (3.8g/kg BW) or saline solution. Mitochondrial function was evaluated 6h after injection (AH onset). At the onset of AH, malate-glutamate and succinate-supported state 4 oxygen uptake was 2.3 and 1.9-fold increased leading to a reduction in respiratory control of 55% and 48% respectively, as compared with controls. Decreases of 38% and 16% were found in Complex I-III and IV activities. Complex II-III activity was not affected by AH. Mitochondrial membrane potential and mitochondrial permeability changes were evaluated by flow cytometry. Mitochondrial membrane potential and permeability were decreased by AH in cerebellum mitochondria. Together with this, AH induced a 25% increase in superoxide anion and a 92% increase in hydrogen peroxide production in cerebellum mitochondria. Related to nitric oxide (NO) metabolism, neuronal nitric oxide synthase (nNOS) protein expression was 52% decreased by the hangover condition compared with control group. No differences were found in cerebellum NO production between control and treated mice. The present work demonstrates that the physiopathological state of AH involves mitochondrial dysfunction in mouse cerebellum showing the long-lasting effects of acute EtOH exposure in the central nervous system.
authors.affiliation: Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
authors.forename: A G
authors.initials: AG
authors.lastname: Karadayian
authors.affiliation: Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
authors.forename: J
authors.initials: J
authors.lastname: Bustamante
authors.affiliation: Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Czerniczyniec
authors.affiliation: Instituto de Bioquímica y Medicina Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
authors.forename: P
authors.initials: P
authors.lastname: Lombardi
authors.affiliation: Instituto de Fisiología y Biofísica Bernardo Houssay, Facultad de Medicina, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
authors.forename: R A
authors.initials: RA
authors.lastname: Cutrera
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Lores-Arnaiz
mesh_terms: D019973:Alcohol-Related Disorders / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D005609:Free Radicals / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects
chemical_list: D000975:Antioxidants; D002492:Central Nervous System Depressants; D005609:Free Radicals; D000431:Ethanol
keywords: Alcohol hangover; Free radicals; Mitochondrial dysfunction; Oxidative stress