Oxidative damage and brain atrophy in alcoholics

Abstract

Emilio Gonzalez-Reimers, Geraldine Quintero-Platt, Camino FernandezRodriguez, Emilio Gonzalez-Arnay, M. Candelaria Martin- Gonzalez, Onan Perez-Hernandez

Generalized brain atrophy, especially affecting frontal lobes, hippocampus and cerebellum, is frequently observed in alcoholics. This alteration leads to cognitive dysfunction (that may affect 50-80% of alcoholics, even young people) and altered gait and movement disorders. Although several factors may contribute, oxidative damage, mainly due to increased production of reactive oxygen species plays an outstanding role in its pathogenesis, and will be reviewed in this manuscript. Among them, we can consider mechanisms directly dependent on ethanol metabolism; mechanisms related to increased cytokine secretion, partly dependent on ethanol-induced increased intestinal permeability, endotoxemia and micro RNA induction; mechanisms related to ethanol-mediated iron overload; mechanisms related to ethanol-derived toxic lipid synthesis; and mechanisms related to altered trace element and vitamin concentrations that can affect antioxidant systems. Despite the role of pro-oxidants, and in contrast with experimental data, no clear-cut benefit has been observed in clinical trials with antioxidants. Alcohol abstinence, together with adequate nutrition, still constitute the most effective therapeutic approach in these patients.