Combined exposure to m-xylene and ethanol: oxidative stress in the rat liver

Ethanol may be a significant combined factor in human solvent toxicity. Lipid peroxidation has been suggested to be an important contributing mechanism involved in experimental alcohol-induced liver injury. The aim of the study was to investigate whether a short-term ethanol ingestion in rats chronically exposed to m-xylene vapor may influence the lipid peroxidation rate in the intracellular hepatic membranes, the level of glutathione and the activity of glutathione-related enzymes in the liver.

Experiments were performed on male Wistar rats (outbred IMP:WIST) exposed to m-xylene (5 months, 5 h/day), at a low concentration (400 mg/m3), and/or acute ethanol administration (6 oral doses of 0.25 g/100 g b.w. at 12 h intervals, for the last 3 days of xylene exposure). To estimate the oxidative stress in the liver, lipid peroxidation rate in microsomal and lysosomal membranes, glutathione sulfhydryls levels, and glutathione-S-transferase activity were determined.

The studies indicated that combined exposure to ethanol and m-xylene, as distinct from the chronic exposure to m-xylene alone, led to the increased lipid peroxidation rate in microsomal and lysosomal membranes with a simultaneous decrease in the levels of glutathione sulfhydryls and glutathione-S-transferase activity.

We conclude that the enhanced lipid peroxidation rate in the intracellular hepatic membranes may be an important agent in combined ethanol/xylene-induced hepatotoxicity.