Reduced cytochrome P450 and increased heme oxygenase in liver during rabbit aflatoxicosis

The administration of aflatoxin B1 (AFB1) in New Zealand rabbit for 5 days at a daily oral dose of 0.05 or 0.1 mg/kg decreased microsomal hepatic cytochrome P450 whereas a dose-dependent increase in the reduced microsomal 420nm absorption occured. The nature of such an absorption was then investigated. Either in vitro incubation of control microsomal proteins with AFB1 up to 800 mu M and NADPH, or primary rabbit hepatocyte cultures exposure to AFB1 up to 30 mu M for 24 to 72h, failed to produce any 420nm absorbing species, suggesting that the 420nm absorption observed in vivo was due to an hemoprotein increase. Chemical reductions of microsomal proteins from AFB1-treated rabbits confirmed this hypothesis. Enzyme activity determinations revealed an increase in both microsomal heme oxygenase and NADPH-cytochrome c reductase activities in AFB1 treated rabbits, suggesting that the 420nm absorption observed in vivo was related to a particular increase in heme oxygenase.