HEPATIC-EFFECTS OF ACUTE LINDANE TREATMENT IN RATS CHRONICALLY FED A HIGH ETHANOL REGIMEN RELATIVELY LOW IN ALPHA-TOCOPHEROL

Our previous results indicated that long-term pretreatment of rats wit h an ethanol regimen high in a-tocopherol did not significantly affect per se the normal balance between prooxidant and antioxidant hepatic factors or influenced the well known prooxidant hepatic effect of acut e lindane administration. The purpose of the present study was to dete rmine whether the long-term consumption by rats of an ethanol regimen relatively low in alpha-tocopherol may produce per se hepatic oxidativ e stress and/or may modify the acute effect of lindane. Male Wistar ra ts (109.58 +/- 3.25 g) were fed ad lib for 11 weeks a basal diet conta ining 2.5 mg % of alpha-tocopherol or the same basal diet plus a 32% e thanol-25% sucrose solution also ad lib, and were then injected i.p. w ith either a single dose of lindane (20 mg/kg) or with an equivalent a mount of corn oil. The results showed that although the chronic consum ption of the ethanol regimen per se decreased the dietary intake of al pha-tocopherol, and produced evidence of hepatic oxidative stress (i.e . increased chemiluminescence and thiobarbituric acid reactive substan ces [TBRS], as well as decreased activities of glutathione peroxidase and superoxide dismutase [SOD]), it did not produce fatty liver or evi dence of liver damage (i.e. normal hepatic triglycerides [TG], histolo gy and activities of serum alanine and aspartate aminotransferases). W hile acute lindane treatment per se (in non-ethanol fed rats) produced a clear prooxidant effect, as denoted by increases in hepatic microso mal content of cytochrome P-450, NADPH-oxidase activity, production of O2-, chemiluminescence, and TBRS, as well as by a decrease in the hep atic activity of SOD, it did not increase the hepatic TG, or produced any histologic evidence of liver damage. On the other hand, acute lind ane administration to ethanol-fed rats did not increase the oxidative stress induced by the ethanol regimen. In conclusion, although under t he conditions of this experiment the long-term pretreatment of rats wi th an ethanol regimen relatively low in alpha-tocopherol may induce pe r se some hepatic oxidative stress, the magnitude of this stress appea red insufficient to damage the liver, or to increase the well establis hed prooxidant effect of lindane. If anything, the chronic consumption ethanol, even with a regimen relatively low in vitamin E, appeared to ameliorate rather than to aggravate the hepatic prooxidant effects of acute lindane treatment.