Effects of Acute Ethanol Administration on Brain Oxidative Status: The Role of Acetaldehyde

Ethanol (EtOH), one of the most widely consumed substances of abuse, can induce brain damage and neurodegeneration. EtOHis centrally metabolized into acetaldehyde, which has been shown to be responsible for some of the neurophysiological and cellular effects of EtOH. Although some of the consequences of chronic EtOHadministration on cell oxidative status have been described, the mechanisms by which acute EtOHadministration affects the brain's cellular oxidative status and the role of acetaldehyde remain to be elucidated in detail. Swiss 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 EtOH(2.5 g/kg, i.p.) administration. Animals were sacrificed 30 minutes after EtOHinjection. Glutathione peroxidase (GPx) mRNAlevels; 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; and protein carbonyl group (CG) content were determined in whole‐brain samples. Acute EtOHadministration enhanced GPx activity and the GSH/GSSGratio, while it decreased GRactivity and GSSGconcentration. Pretreatment with DPor LAonly prevented GPx activity changes induced by EtOH. Altogether, these results show the capacity of a single dose of EtOHto unbalance cellular oxidative homeostasis. Consequences of chronic ethanol (EtOH) administration on cell oxidative status have been described. However, effects of acute EtOH administration on brain oxidative status and the role of acetaldehyde remain to be elucidated in detail. Here we demonstrated the capacity of a single dose of EtOH to unbalance cellular oxidative homeostasis by enhancing glutathione peroxidase (GPx) activity and the reduced glutathione / oxided glutathione (GSH/GSSG) ratio. Pretreatment with D‐penicillamine (DP) or lipoic acid (LA) only prevented GPx activity changes induced by EtOH.