Effects of Aliphatic Chlorohydrocarbons on Drug-metabolizing Enzymes in Rat Liver in vivo

Abstract

1. Various polychlorinated hydrocarbons were administered intragastrically to rats to examine their effects on the biotransformation capacity of the liver. Due to high toxicity, 1,1,2,2-tetrachloroethane and pentachloroethane were given at a dose level equivalent to one quarter of that of CCl₄ and the other chlorohydrocarbons (i.e. 2.6 mmol/kg).

2. Carbon tetrachloride at 10.3 mmol/kg was the most active in decreasing cytochrome P-450 content and the overall drug hydroxylation activities in rat liver. 1,1,2,2-Tetrachloroethane was the next most active in decreasing the hepatic drug oxidizing enzymic activities.

3. Epoxide hydratase activity in rat liver declined significantly after CCl₄, 1,1,2,2-tetrachloroethane and pentachloroethane administrations.

4. UDP-Glucuronosyltransferase was affected to a lesser extent than the microsomal mono-oxygenase or epoxide hydratase by chlorohydrocarbon treatment.