Effects of acute ethanol administration on brain oxidative status: the role of acetaldehyde.

Abstract

INTRODUCTION\nEthanol, one of the most widely consumed substances of abuse, can induce brain damage and neurodegeneration. Ethanol is centrally metabolized into acetaldehyde, which has been shown to be responsible for some of the neurophysiological and cellular effects of ethanol. Although some of the consequences of chronic ethanol administration on cell oxidative status have been described, the mechanisms by which acute ethanol administration affects the brain s cellular oxidative status and the role of acetaldehyde remain to be elucidated in detail.\n\n\nMETHODOLOGY\nSwiss CD-I mice were pretreated with the acetaldehyde-sequestering agent D-penicillamine (DP) (75 mg/kg, i.p.) or the antioxidant lipoic acid (LA) (50 mg/kg, i.p.) 30 minutes before ethanol (2.5 g/kg, i.p.) administration. Animals were sacrificed 30 minutes after ethanol injection. Glutathione peroxidase (GPx) mRNA levels, GPx and glutathione reductase (GR) enzymatic activities, reduced glutathione (GSH), glutathione disulfide (GSSG), glutamate, g-L-glutamyl-L-cysteine (Glut-Cys), and malondialdehyde (MDA) concentrations, as well as protein carbonyl group (CG) content were determined in whole brain samples.\n\n\nRESULTS\nAcute ethanol administration enhanced GPx activity and the GSH/GSSG ratio, while decreased GR activity and GSSG concentration. Pretreatment with DP or LA only prevented GPx activity changes induced by ethanol.\n\n\nCONCLUSIONS\nAll together, these results show the capacity of a single dose of ethanol to unbalance cellular oxidative homeostasis. This article is protected by copyright. All rights reserved.