EFFECTS OF DIMETHYL DIPHENYL BICARBOXYLATE ON THE METABOLISM AND HEPATOTOXICITY OF AFLATOXIN B₁IN RATS

AIMTo study the effect of antihepatitis drug, dimethyl diphenyl bicarboxylate (DDB) on the metabolism and hepatotoxicity of aflatoxin B₁(AFB₁) in rats. METHODSRats were given orally DDB 300 mg·kg^-1·d^-1 for 3 days and then injected intraperitoneally with AFB₁1.5 mg·kg^-1. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined 16 hours after the injection of AFB₁. The in vitro metabolism of AFB₁by DDB-pretreated rat liver microsome was investigated by HPLC assay. RESULTS DDB (300 mg·kg^-1) pretreatment provided significant protection against AFB₁hepatotoxicity as evidenced by the decrease of AFB₁-elevated serum marker enzymes in rats. Pretreatment with DDB was shown to slightly increase the level of AFM₁, the less toxic metabolite. DDB significantly increased the liver cytochrome P450 content, P450 isozyme 2B₁-mediated 7-pentoxyresorufin O-dealkylase (PROD) activity, cytosolic glutathione (GSH) level and GSH S-transferase (GST) activities. In addition, DDB slightly increased P450 isozymes, 3A-mediated erythromycin-demethylase and 1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activities. CONCLUSIONThe results indicate that DDB protected rats against AFB₁hepatotoxicity by increasing the detoxifying metabolism of AFB₁in the liver.