POTENTIATION OF AFLATOXIN B₁ INDUCED HEPATOTOXICITY IN MALE WISTAR RATS WITH ETHANOL PRETREATMENT

Abstract

The interaction of ethanol and aflatoxin B₁ (AFB₁)-induced hepatotoxicity was studied in male Wistar rats using the activity of plasma GOT and GPT, liver triglyceride and histopathologic changes of liver necrosis as indices. Pretreatment of four oral doses of ethanol (4.0 g/kg BW each) at 48, 45, 24 and 21 hrs prior to AFB₁ (0.5 to 2.0 mg/kg BW) single i.p. administration caused a significant increase in the activity of PGOT (6 folds) and PGPT (5 folds), liver triglycerides (2 folds) and severity of liver necrosis at 48 hrs after AFB₁ administration. Ethanol pretreatment potentiated AFB₁-induced hepatotoxicity by increasing MFO enzymes, aniline hydroxylase and P-nitroanisole-O-demethylase activity and lipid peroxidation, and decreasing in cytochrome b₅, epoxide hydrolase activity and hepatic glutathione content. However, it did not cause any significant change in the activity of NADPH-cytochrome c reductase and glutathione-S-transferase and cytochrome P-450. These results suggest that potentiation of ethanol pretreatment on AFB₁-induced hepatotoxicity may due to an increase in the metabolic formation of AFB₁-2, 3-oxide and subsequent binding to DNA.