Differential in vivo effects of α-naphthoflavone and β-naphthoflavone on CYP1A1 and CYP2E1 in rat liver, lung, heart, and kidney

Male Sprague-Dawley rats were treated intraperitoneally with corn oil, the aryl hydrocarbon receptor (AHR) agonist beta-naphthoflavone (beta NF), or the relatively weak AHR agonist alpha-naphthoflavone (alpha NF). Animals treated with beta NF experienced a significant loss (12%) of total body mass over 5 days and a dramatic elevation of CYP1A1 mRNA in all of the organs studied. Treatment with alpha NF had no significant effect on body mass after 5 days and caused only minor increases of liver, kidney, and heart CYP1A1 mRNA. In contrast, lung CYP1A1 mRNA was increased by alpha NF treatment to levels comparable to that seen with beta NF treatment. CYP2E1 mRNA levels were also elevated in liver, lung, kidney and heart in response to beta NF treatment, whereas alpha NF was without effect. Large increases of CYP1A1-dependent 7-ethoxyresorufin O-deethylation (EROD) activity occurred with microsomes prepared from the tissues of beta NF-treated animals. Comparatively small changes were associated with alpha NF treatment, with the exception of lung, where EROD activity was increased to approximately 60% of that with beta NF treatment. CYP2E1-dependent p-nitrophenol hydroxylase (PNP) activity was also increased by beta NF treatment in microsomes prepared from kidney (3.1-fold), whereas alpha NF was without effect. In contrast, alpha NT or beta NF treatment caused significant decreases of lung microsomal beta NF (72% and 27% of corn oil control, respectively) and 7-pentoxyresorufin O-deethylation (48% and 17% of corn oil control, respectively) activities, indicating that PNP activity may be catalyzed by F450 isoforms other than CYP2E1 in rat lung. We conclude that beta NF and alpha NF have differential effects on the expression and catalytic activity of CYP1A1 and CYP2E1, depending upon the organ studied. These changes most likely occur as a result of the direct actions of these compounds as AHR agonists, in addition to secondary effects associated with AHR-mediated toxicity. (C) 1998 John Wiley & Sons, Inc.