Hepatic mitochondrial function and lysosomal enzyme activity in ethanol-potentiated aflatoxin B 1 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.