Relationship between changes of drug metabolizing enzyme activities and toxicity following pentachlorobenzene administration in rats.

Abstract

To investigate the relationship between pentachlorobenzene toxicity and the changes of hepatic drug metabolizing enzyme activities, various doses of pentachlorobenzene were administered to rats for 5 days. Both cytochrome P-450 content and UDP-glucuronyltransferase activity increased with an increase in the dose up to 160 mg/kg. However, at the dose of 250 mg/kg, there was no further increase in UDP-glucuronyltransferase activity but a significant decrease in cytochrome P-450 content. In contrast, glutathione S-transferase activity was slightly but significantly increased up to the dose of 250 mg/kg. Glutathione S-transferase activity was inversely correlated with glutathione content in the liver. Content of pentachlorobenzene in the liver linearly increased up to 160 mg/kg, and was markedly enhanced at the dose of 250 mg/kg. Accumulative patterns of pentachlorobenzene in the brain and kidney were similar to that in the liver, while those in adipose tissues were quite different from that in the liver. In adipose tissues, pentachlorobenzene content was 8-27 times higher than that in the liver and the content linearly increased up to 250 mg/kg. A main metabolite of pentachlorobenzene in the liver was pentachlorophenol.