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ORIGINAL RESEARCH ARTICLE

Soy Protein Isolate Induces CYP3A1 and CYP3A2 in Prepubertal Rats

Martin J. Ronis^*,,1,1, Ying Chen^*,, Jamie Badeaux^*, Elizabeth Laurenzana and Thomas M. Badger^*,

^* Arkansas Children’s Nutrition Center, Department of Pharmacology & Toxicology, and Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205

To whom requests for reprints should be addressed at ¹ Arkansas Children’s Nutrition Center, 1120 Marshall Street, Little Rock, AR 72202. E-mail: ronismartinj{at}uams.edu

Feeding soy diets has been shown to induce cytochrome P450s in gene family CYP3A in Sprague-Dawley rat liver. We compared expression of CYP3A enzymes on postnatal Day 33 (PND33) rats fed casein or soy protein isolate (SPI+)–based AIN-93G diets continuously from gestational Day 4 through PND33 or the diets were switched on PND15 (n = 3–6 litters) to examine the potential imprinting effects of soy on drug metabolism. In addition rats were fed casein, SPI+, SPI+ stripped of phytochemicals (SPI–), or casein diets supplemented with the soy-associated isoflavones genistein or daidzein from weaning through PND33 to examine the hypothesis that the isoflavones are responsible for CYP3A induction by soy feeding. Feeding SPI either continuously or from weaning induced hepatic CYP3A1 and CYP3A2 mRNA, apoprotein, and CYP3A-dependent testosterone 6ß-hydroxylase activity in liver microsomes 2- to 5-fold (P < 0.05). CYP3A mRNA expression was also elevated 2- to 3-fold in the jejunum of SPI-fed rats (P < 0.05). CYP3A was not induced in livers of rats switched to casein from soy at weaning. Induction of CYP3A1 also did not occur in rats fed SPI–, but CYP3A2 mRNA and apoprotein were induced (P < 0.05) in females fed SPI–. Offspring weaned onto genistein-supplemented diets had no elevation of CYP3A mRNAs or apoproteins. Weaning onto daidzein diets increased CYP3A2 mRNA and apoprotein expression in male rats (P < 0.05). These data suggest that early soy consumption may increase the metabolism of a wide variety of CYP3A substrates, but that soy does not imprint the expression of CYP3A enzymes. Effects on CYP3A1 expression appear to be primarily due to phytochemical components of SPI other than isoflavones. In contrast, consumption of soy protein and daidzein appear to be associated with the induction of CYP3A2.

Key Words: soy protein isolate • CYP3A • isoflavones • rat • weaning