Multiple Effects and Metabolism of α-Naphthoflavone in Induced and Uninduced Hepatic Microsomes
α-Naphthoflavone (7,8-benzoflavone [ANF])(see Figure 1) has been reported to elicit multiple effects with regard to the mixed-function oxidase enzymes that metabolize drugs, steroids, and xenobiotics (1). These effects -- enzyme induction, enzyme inhibition, and enzyme activation -- seem to occur by different mechanisms in the mammalian species studied. ANF has been reported to be a less effective inducer of cytochrome P-448-mediated hepatic mixed-function oxidases in rats than its isomer ß-rnaphthoflavone (BNF) (2). ANF is a potent inhibitor of 3-methylcholanthrene (3-MC)-induced or BNF-induced rat liver microsomes (cytochrome P-448) and was first described by Diamond and Gelboin (3) and Wiebel et al. (2). In addition, ANF is found to have no inhibitory effect on the mixed-function oxidases from phenobarbital (PB)-induced rat liver (cytochrome P-450) (2,4). In fact, ANF stimulates or activates these enzymes (2,4). This activation phenomenon is also observed in hepatic preparations from untreated rats, mice, rabbits, and humans (1). The mechanisms by which ANF activates or inhibits the mixed-function oxidases were of interest to us, and we began a series of investigations to try to elucidate them. This paper reviews these previous and present investigations and presents new findings that may help to explain the multiple effects of ANF observed in mammalian hepatic tissues.
KeywordsMicrosomal Protein Hepatic Microsome Monooxygenase Activity Hamster Liver Microsomal Enzyme Activity
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