Altered expression and glucocorticoid-inducibility of hepatic CYP3A and CYP2B enzymes in male rats fed diets containing soy protein isolate.
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 6beta-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.
Ronis
M J
MJ
Arkansas Children's Nutrition Center, Arkansas Children's Hospital Research Institute and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Rowlands
J C
JC
Hakkak
R
R
Badger
T M
TM
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001835:Body Weight / Q000187:drug effects; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology*; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004044:Dietary Proteins / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D030262:Soybean Proteins / Q000008:administration & dosage / Q000494:pharmacology*
D002364:Caseins; D004044:Dietary Proteins; D005938:Glucocorticoids; D030262:Soybean Proteins; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating