Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/9/2005
Publication Date: 4/25/2006
Citation: Ronis, M.J., Chen, Y., Badeaux, J., Laurenzana, E., Badger, T.M. 2006. Soy protein isolate induces CYP3A1 and CYP3A2 in prepubertal rats. Experimental Biology and Medicine. 231(1):60-69.
Interpretive Summary: Liver enzymes called CYP3As are responsible for the metabolism and clearance of the majority of pediatric medications. In the current study we examined CYP3A enzymes in Sprague-Dawley rats fed diets containing soy protein and/or two components of soy protein called isoflavones (genistein and daidzein). The rats were fed the diets for age 15 days to age 33 days to simulate the time human infants would be fed soy formula. Feeding soy protein-containing diets increased CYP3A relative to offspring fed non-soy diets. However, these effects occurred only when the soy protein contained the isoflavone daidzein. These data suggest that early soy consumption may alter the metabolism of some pediatric medications. This is important in the medical management of infants, and we are continuing to study these effects in animals and in human infants.
Technical Abstract: 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 PND33 rats fed casein or soy protein isolate (SPI+)-based AIN-93G diets continuously from gestational day 4 through PND 33 or the diets were switched on PND 15 (n = 3-6 litters) to examine 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 PND 33 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 6b-hydroxylase activity in liver microsomes 2-5-fold (p < 0.05). CYP3A mRNA expression was also elevated 2-3-fold in the jejunum of SPI-fed rats (p < 0.05). CYP3As were 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 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 the soy protein and daidzein appear to be associated with induction of CYP3A2.