Enhanced inhibition of hepatic microsomal calcium pump activity by CCl4 treatment of isopropanol-pretreated rats.

Pretreatment of rats with isopropanol enhanced both hepatotoxicity and calcium pump inhibition after CCl4 exposure in vivo or in vitro. Animals were given isopropanol (1.25 ml/kg) 18 hr before CCl4 (0.01 to 1.0 ml/kg). CCl4 hepatotoxicity, judged as increased appearance of glutamic-pyruvate transaminase in serum, was enhanced by isopropanol pretreatment. Pretreatment of rats with isopropanol made CCl4 as much as 20- to 30-fold more potent as an inhibitor of the calcium pump. Inhibition of another endoplasmic reticulum enzyme, glucose 6-phosphatase, was also enhanced by isopropanol pretreatment. In contrast to the effect of CCl4 in control animals, in isopropanol-pretreated rats given CCl4, depletion of liver glutathione was observed. Altered CCl4 metabolism in isopropanol-pretreated animals may result in production of increased amounts of phosgene (or other metabolites) responsible for inhibition of the liver microsome calcium pump and glutathione depletion.