IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Residual effect of acute ethanol exposure on mitochondrial physiology in mouse cortex and cerebellu
Autor/es:
KARADAYIAN, AG; CZERNICZYNIEC, A; LOMBARDI, PAULINA; BUSTAMANTE, J.; LORES ARNAIZ, S
Lugar:
Rio de Janeiro
Reunión:
Congreso; 9º World Congress of the International Brain Research Organization; 2015
Resumen:
Excessive alcohol consumption causes a number of serious consequences to health. Binge drinking behavior is the most common drinking form among adolescents and young adults. The alcohol hangover is a transient state that includes unpleasant psychophysical symptoms as a result of the residual effect of acute alcohol intake. Acute ethanol exposure induces the production of active oxygen species associated with mitochondrial dysfunction. However, the residual effect of acute ethanol exposure in mitochondrial bioenergetics is still unknown. The aim of this work was to study the mitochondrial function and the production of active oxygen species at the beginning of alcohol hangover in brain cortex and cerebellum. Swiss male mice were treated with a single i.p. injection of saline (control group) or ethanol (3.8 g/kg; hangover group). The study of mitochondrial bioenergetics was performed 6 h post-treatment when the blood alcohol concentration was close to zero (hangover start). Results showed a significant decrease in mitochondrial respiratory control both in brain cortex and cerebellum as a consequence of the residual effect of ethanol exposure. Specifically, the hangover group showed a significant decrease in state 3 respiration rates in brain cortex mitochondria while a significant increase in the state 4 was found in cerebellum. Associated to the reduction in oxygen uptake, changes in mitochondrial membrane potential were found. Specifically, transmembrane potential was 20% decreased in brain cortex and 50% decreased in cerebellum mitochondria. The enzymatic activity of the mitochondrial respiratory complexes was significantly reduced in both areas due to the hangover condition. Particularly, the activity of complex I-III, II-III and IV was 19%, 36% and 42% decreased in brain cortex respectively and decreases of 38% and 16% were observed in the activity of complex I-III and IV in cerebellum respectively. Together with the mitochondrial dysfunction, a significant increase in free radicals production was observed. Indeed, alcohol hangover induced increases of 17% and 28% in superoxide anion production in brain cortex and cerebellum respectively while hydrogen peroxide production was 90% higher in both areas at the beginning of a hangover. Related to NO metabolism, alcohol hangover induced a 25% decrease in NO production by both nNOS and iNOS enzymes activity, however, no significant changes in NO production was found in cerebellum. Based on these findings, it is postulated that mitochondrial dysfunction in the Central Nervous System together with the imbalance in the cellular redox homeostasis could play a relevant role in the pathophysiological alterations during alcohol hangover.