Effects of bicyclol on aflatoxin B1 metabolism and hepatotoxicity in rats

Acta Pharmacol Sin. 2002 Oct;23(10):942-5.

Abstract

Aim: To study the effect of new antihepatitis drug, bicyclol, on the metabolism and hepatotoxicity of aflatoxin B1 (AFB1) in rats.

Methods: Rats were given bicyclol 300 mg/kg/d ig for 3 d and then injected ip with AFB1 1.5 mg/kg. Liver damages were examined 16 h after ip AFB1. The in vitro metabolism of AFB1 by bicyclol-pretreated liver microsomes was investigated by HPLC assay.

Results: Bicyclol (300 mg/kg/d for 3 d) pretreatment provided protection against AFB1 hepatotoxicity as evidenced by the decrease of AFB1-elevated serum aminotransferase and hepatic malondialdehyde in rats. Bicyclol pretreatment slightly increased the production of the less toxic metabolite aflatoxin Q1. Bicyclol increased liver cytochrome P450 content, CYP 2B1-mediated 7-pentoxyresorufin O-dealkylase (PROD) activity, cytosolic glutathione (GSH) level, and GSH S-transferase (GST) activities. Moreover, bicyclol increased CYP 3A-mediated erythromycin-demethylase and CYP 1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activities.

Conclusion: Bicyclol protected rats against AFB1 hepatotoxicity by increasing the detoxifying metabolism of AFB1 in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aflatoxin B1 / metabolism
  • Aflatoxin B1 / toxicity*
  • Animals
  • Biphenyl Compounds / therapeutic use*
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Drug Interactions
  • Inactivation, Metabolic
  • Male
  • Rats
  • Rats, Wistar

Substances

  • Biphenyl Compounds
  • Cytochrome P-450 Enzyme System
  • bicyclol
  • Aflatoxin B1