Prolonged phenobarbital pretreatment abolishes the early oxidative stress component induced in the liver by acute lindane intoxication

Abstract

Lindane administration to rats (60 mg/kg b.w.) led to an enhancement in the oxidative stress status of the liver at 4 h after treatment, characterized by increases in hepatic thiobarbituric acid reactants (TBARS) formation and chemiluminescence, reduced glutathione (GSH) depletion, and diminution in the biliary content and release of GSH. These changes were observed in the absence of changes in either microsomal functions (cytochrome P450 content, NADPH-dependent superoxide radical production, and NADPH-cytochrome P450 reductase or NADPH oxidase activities) or in oxidative stress-related enzymatic activities (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and glutathione- S-transferases), over control values. Phenobarbital (PB) administration (0.1% in drinking water; 15 days) elicited an enhancement in liver microsomal functions, lipid peroxidation, and GSH content, without changes in oxidative stress-related enzymatic activities, except for the elevation in those of glutathione reductase and glutathione- S-transferase, compared to control rats. Lindane given to PB-pretreated rats did not alter liver microsomal functions, lipid peroxidation, glutathione status, or oxidative stress-related enzymatic activities, as compared to PB-pretreated animals. In addition, lindane induced periportal necrosis with hemorrhagic foci in untreated rats, but not in PB-pretreated animals. It is concluded that the early oxidative stress response of the liver to lindane and hepatic injury are suppressed by PB pretreatment via induction of microsomal enzymes in all zones of the hepatic acinus.