PROOXIDANT AND ANTIOXIDANT HEPATIC FACTORS IN RATS CHRONICALLY FED ANETHANOL REGIMEN AND TREATED WITH AN ACUTE DOSE OF LINDANE

While acute lindane treatment and chronic ethanol feeding to rats have been associated with hepatic oxidative stress, the possible roles of these stresses in the pathogenesis of hepatic lesions reported in acut e lindane intoxication and in those observed in some models of chronic alcoholism have not been established. Our previous studies in rats ch ronically fed ethanol regimens and then treated with a single intraper itoneal (ip) dose of lindane (20 mg/kg) showed that while lindane per se was invariably associated with hepatic oxidative stress, chronic et hanol feeding only produced this stress when the dietary level of vita min E was relatively low. Chronic ethanol pretreatment did not signifi cantly affect the lindane-associated oxidative stress, and neither chr onic ethanol feeding nor acute lindane, single or in combination, prod uced any histologic and biochemical evidence of liver damage. In the p resent experiment, the acute dose of lindane was increased to 40 mg/kg , and we have studied a larger number of prooxidant and antioxidant he patic factors. Male Wistar rats (115.5 +/- 5.4 g) were fed ad lib for II weeks a calorically well-balanced and nutritionally adequate basal diet, or the same basal diet plus a 32% ethanol/25% sucrose solution, also ad lib, and were then injected ip with a single dose of lindane o r with equivalent amounts of corn oil. The results indicated that acut e lindane treatment to naive rats increased practically all the prooxi dant hepatic factors examined (cytochromes P450 and b(5), NADPH cytoch rome c reductase, NADPH oxidase), as well as the generation of microso mal superoxide radical and thiobarbituric acid reactive substances of liver homogenates, but did not modify any of the antioxidant hepatic f actors studied. Conversely, the chronic administration of ethanol alon e did not significantly affect the prooxidant hepatic factors but redu ced some of the antioxidants (i.e., the activities of GSH-Px and the c ontents of alpha-tocopherol and ubiquinols 9 and 10). Although chronic ethanol pretreatment further increased the superoxide generation indu ced by lindane per se, it did not increase but generally reduced the e ffects of lindane per se on the other prooxidant factors studied. Furt hermore, although acute lindane administration to ethanol-pretreated r ats was associated with decreases in GSH and catalase (not affected by ethanol or lindane treatment alone), it did not substantially modify the reducing effects of ethanol feeding per se on GSH-Px, alpha-tocoph erol, and ubiquinols. Once again, neither chronic ethanol feeding nor lindane treatment, single or in combination, was associated with any e vidence of liver damage.