Dose- and Time-Dependent Effects of Ethanol on Plasma Antioxidant System in Rat

This study investigates the dose- as well as time-dependent effects of ethanol ingestion on antioxidant system and lipid peroxidation in plasma of the rat. The plasma ethanol concentrations were 154 ± 18, 231 ± 53, and 268 ± 49 mg/dl 1 h after oral ethanol doses of 2, 4, and 6 g/kg, respectively. Superoxide dismutase (SOD) (71%, 56%, and 41% of control) and glutathione reductase (GR) (71%, 66%, and 55% of control) activity in plasma were significantly decreased in a dose-dependent manner. Catalase (CAT)/SOD and glutathione peroxidase (GSH-Px)/SOD ratios were significantly increased whereas GR/GSH-Px ratio was significantly decreased with increasing dose of ethanol. In a time course study, plasma ethanol concentrations were 177± 9.7, 143± 11, 99± 17, and 26± 11 mg/dl at 1.5, 2, 4, and 6 h after an oral dose (4 g/kg) of ethanol in rat indicating time-dependent elimination of ethanol. Plasma SOD and GSH-Px activity significantly increased 4–6 h whereas GR activity significantly decreased 2–4 h after ethanol ingestion. The ratio of GR/GSH-Px and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in plasma decreased at 1.5–6 h after ethanol ingestion. Plasma malondialdehyde (MDA) levels significantly elevated with respect to an increase in time after ethanol ingestion, indicating time-dependent augmentation of lipid peroxidation. The data indicate that ethanol ingestion perturbs the plasma antioxidant system in a dose- and time-dependent manner. The significant changes in the ratios of CAT/SOD, GSH-Px/SOD, GR/GSH-Px, and GSH/GSSG in plasma may be used as an index of alcohol-induced oxidative stress.