Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 1/15/2003
Publication Date: 3/14/2003
Citation: RONIS, M., HARDY, H., CURTIS, C., REEVES, M., BADEAUX, J., FERGUSON, M., DALLARI, T., BADGER, T.M. Induction of CYP3A1 and CYP3A2 in the Liver of Rats Weaned onto Soy Protein Isolate (SPI) from Casein (CAS).. JOURNAL OF FEDERATION OF AMERICAN SOCIETIES FOR EXPERIMENTAL BIOLOGY. 2003. v. 17(4). p. A333. Abstract No. 203.5. Interpretive Summary: We have previously shown that feeding the soy protein isolate used to make soy-based infant formula to rats during development results in increased expression of a family of liver enzymes, the CYP3As. Removal of most medications from the body start with the CYP3A enzymes, so alteration in CYP3A levels in the liver and intestine can alter the time it takes to clear a drug from the body and tissue concentrations produced by a particular dose (drug efficacy). Altered CYP3A levels may also change the risk of side effects or of toxic drug/drug interactions. The present study was conducted in rats to determine if the effects of feeding soy on CYP3A are direct effects of dietary components or are associated with altered developmental processes such as metabolic imprinting. Feeding soy diets high in isoflavones increased the levels of two different CYP3A enzymes, CYP3A1 and CYP3A2. In contrast, soy diets very low in isolfavones only increased CYP3A2 levels. No effects were seen with genistein (the major soy isolfavone) supplemented diets, but daidzein (a second major soy isoflavone) supplementation increased both CYP3A enzymes. Therefore, soy feeding directly increases liver levels of CYP3As and daidzein may be the most important component of soy involved in this effect. These data suggest that feeding soy infant formula may increase CYP3A expression in infants relative to those fed milk-based formula or breast fed and that this might alter the efficacy of pediatric medications such as antibiotics in these infants.
Technical Abstract: We examined induction of CYP3A expression in weaning rats fed SPI. N = 8-10 time-impregnated Sprague-Dawley rats were placed on casein diets on gestational day 4 and fed CAS through the end of weaning. Diet pellets containing CAS, SPI, and low-isoflavone-SPI (SPI-) and CAS supplemented with either genistein (CAS + GEN) or daidzein (CAS + DAID) at levels equivalent to those found in SPI were placed in the cage starting on postnatal day 15 and pups were weaned to that diet. All pups were sacrificed at age 33 days. CYP3A apoprotein was measured in liver microsomes by Western blot and CYP3A1 and CYP3A2 mRNA levels assessed by real time RT-PCR. Feeding SPI induced CYP3A apoprotein, CYP3A1 and CYP3A2 mRNA (p < 0.05) relative to pups fed CAS. Induction of CYP3A mRNAs were greater in male than female pups fed SPI. Induction of CYP3A1 mRNA did not occur in pups fed SPI- but CYP3A2 mRNA was increased in these animals (p < 0.05). Pups weaned onto CAS + GEN had no elevation of CYP3As. However, pups weaned onto CAS + DAID had induced CYP3A1 and CYP3A2 mRNA levels (p < 0.05). Therefore, increases in CYP3A enzymes in weanling rat liver is the result of direct effects of feeding SPI. Effects on CYP3A1 mRNA expression appear to be partially due to daidzein while induction of CYP3A2 mRNA appears to be the result of both daidzein and soy protein components in SPI. Supported in part by USDA ARS CRIS6251-5100-02S.