Altered Expression and Glucocorticoid-Inducibility of Hepatic CYP3A and CYP2B Enzymes in Male Rats Fed Diets Containing Soy Protein Isolate

Abstract

Hepatic CYP3A and CYP2B enzymes were studied in male Sprague-Dawley rats derived from 5–7 litters fed diets in which the protein source was either casein or soy protein isolate. At age 65 d, rats were gavaged with corn oil (vehicle) or 50 mg/kg dexamethasone. Hepatic expression of CYP3A and CYP2B1 mRNA, apoprotein and associated monooxygenase activities were measured. Consumption of soy diets significantly increased monooxygenase activity toward the following: the CYP3A substrates erythromycin and ethylmorphine N-demethylase; corticosterone and testosterone 6β-hydroxylase; and apoprotein and mRNA expression of CYP3A2 (P < 0.05). Dexamethasone significantly induced turnover of erythromycin and testosterone, expression of CYP3A apoprotein, and expression of CYP3A1 and CYP3A2 mRNA (P < 0.05). In addition, significant diet-inducer interactions were observed in the expression of CYP3A apoprotein and activities toward ethylmorphine, corticosterone and testosterone (P < 0.05). Significant diet-inducer interactions were also observed on CYP2B1-dependent pentoxyresorufin O-depentylase activity (P < 0.05). However, although dexamethasone significantly induced CYP2B1 expression at the apoprotein and mRNA level (P < 0.05), no significant diet effects were observed. These data suggest potential effects of soy consumption on the metabolism of a wide variety of CYP3A and CYP2B1 substrates, especially in situations involving coexposure to CYP inducers.