Role of reactive oxygen intermediates in the hepatotoxicity of endotoxin

Abstract Administration of endotoxin (2.5 μg/mouse, iv) to Corynebacterium parvum -pretreated (14 days earlier, 1 mg/mouse, i.v.) mice caused a rapid (90 min) decrease in liver cytochrome P450-dependent drug metablism and an elevation of serum transaminase. The time course of the priming effect of C. parvum suggested that macrophages might be responsible for this sensitization to endotoxin. The antioxidant N -acetylcysteine (500 mg/kg) effectively protected against this depression of liver drug metabolism, thus supporting the hypothesis that liver macrophage-generated free radicals might mediate this hepatoxic effect of endotoxin.