In vitro interaction of AFB1 with rabbit liver monooxygenase activities

The purpose of this study was to determine the influence of aflatoxin B1 (AFB1), incubated in vitro with rabbit liver microsomes, on some cytochrome P450-dependent monooxygenases activities. A strong competitive inhibition of the mycotoxin on aniline hydroxylation was observed. The concentration which provoked a 50% inhibition (IC50) was around 20 microM, whereas a Ki of 3 microM was determined. In contrast, only weak inhibitions of both pentoxyresorufin and ethoxyresorufin O-dealkylases (PROD and EROD) activities were obtained. They were characterized by respective IC50 of 200 and 260 microM. The inhibition was 'non competitive' for PROD activity and 'mixed' for EROD. The Ki of the reactions were respectively 177 and 510 microM. Considering the fact that AFB1 has been previously reported to decrease microsomal hepatic cytochrome P450 expression, the results obtained in this study strengthen the hypothesis that the normal metabolism of xenobiotics by the liver could be altered in AFB1 exposure.