Hepatic mitochondrial function and lysosomal enzyme activity in ethanol-potentiated aflatoxin B1 hepatotoxicity

Abstract

The possible role of hepatic mitochondrial function and lysosomal enzyme activity in ethanol-enhanced aflatoxin B 1 (AFB 1 ) hepatotoxicity was studied in male rats. Hepatic ATP content was significantly decreased in rats treated with ethanol (4.0 g/kg body wt.) and AFB 1 (2.0 mg/kg body wt.) compared with rats treated with AFB 1 alone at 12-72 h after AFB 1 administration. The decrease in hepatic ATP content was due to the decrease in the activity of NADH-cytochrome c reductase whereas cytochrome oxidase activity did not differ in rats treated with ethanol and AFB 1 when compared to AFB 1 alone. Total and free activities of hepatic lysosomal enzymes (glucuronidase, arylsulfatase and acid phosphatase) were significantly increased in rats treated with ethanol and AFB 1 at 24-36 h after AFB 1 administration when compared to AFB 1 alone. The increase in hepatic lysosomal enzyme activities correlated well with the increase in the lipid peroxide level of lysosomes in rats treated with ethanol and AFB 1 . These findings indicate that the decrease in hepatic mitochondrial respiratory enzyme activities and the increase in lipid peroxide level of lysosomes might lead to a decrease in hepatic ATP content, and that the increase in the activities of hepatic lysosomal enzymes, respectively, enhance the AFB 1 hepatotoxicity of ethanol. © 1990.