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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #182236
Title: DIETS CONTAINING SOY PROTEIN ISOLATE INCREASE HEPATIC CYP3A EXPRESSION AND INDUCIBILITY IN WEANLING MALE RATS EXPOSED DURING EARLY DEVELOPMENT

Author
item RONIS, MARTIN - UAMS/ACNC
item CHEN, YING - UAMS/ACNC
item JO, CHAN - UAMS
item SIMPSON, PIPPA - UAMS
item BADGER, THOMAS - UAMS/ACNC

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/15/2004
Publication Date: 12/15/2004
Citation: Ronis, M.J., Chen, Y., Jo, C.H., Simpson, P.A., Badger, T.M. 2004. Diets containing soy protein isolate increase hepatic cyp3a expression and inducibility in weanling male rats exposed during early development. Journal of Nutrition. 134(12):3270-3276.

Interpretive Summary: Over one million American infants are fed soy formula each year. This practice first started in infants who were thought to have milk allergies or other complications that prevented them from consuming milk products. However, many parents prefer soy formula for its potential health benefits, and now over 25% of American infants are fed soy formula. Some critics feel that soy formula is not healthy and we have been studying the effects of soy throughout the lifecycle in rodents, pigs and humans. In this study of rats, we found baby rats that had been exposed to soy from shortly after conception (prior to birth and during lactation because of maternal consumption) had increased levels of some enzymes and these enzymes appeared earlier in life than in rats fed milk proteins. This is interesting and could have many beneficial effects as well as some potential unwanted effects. The enzymes belong to the CYP3A family and they are responsible for breakdown of most of the medications used in pediatric medicine. Therefore, having higher levels of these enzymes could require more medication to maintain the desired efficacy of a particular drug. We are currently conducting a study in human infants.

Technical Abstract: Hepatic CYP3A enzymes were studied in weanling male Sprague-Dawley rats exposed to diets from gestational d 4 in which the sole protein source was either casein (CAS) or soy protein isolate (SPI). At age 25 d, rats were gavaged with corn oil or one of the CYP3A inducers, dexamethasone (DEX) and clotrimazole (CLT), at a dose of 50 mg/kg. Little CYP3A1 (CYP3A23), CYP3A2, or CYP3A9 mRNA was observed in CAS-fed weanling rats but CYP3A18 mRNA was readily detectable in Northern blots. In contrast, consumption of SPI without inducer treatment resulted in the expression of CYP3A1 (CYP3A23), and CYP3A2 mRNAs, expression of CYP3A apoprotein in hepatic microsomes, and a 2-fold greater turnover of the CYP3A substrate midazolam (P < 0.05). DEX induced CYP3A1, CYP3A2, and CYP3A9 (P < 0.05), but not CYP3A18 mRNA expression in rats fed both diets. Hepatic CYP3A apoprotein expression and midazolam 4-hydroxylation in SPI-fed rats was greater than that of CAS-fed rats after DEX treatment (P < 0.05). CLT also induced CYP3A2 mRNA 2-fold in rats fed both diets but CYP3A apoprotein expression in microsomes from SPI-fed CLT rats was double that of CLT-treated rats fed CAS (P < 0.05). The elevation of CYP3A apoprotein due to SPI and the CYP3A apoprotein induction by DEX and CLT treatment yielded no significant diet x inducer interaction. Analysis of heterologous nuclear RNA expression by RT-PCR using intron-specific primers for CYP3A1 revealed a 14-fold increase in RNA transcription in CAS-fed rats after treatment with DEX (P < 0.05) but no increase in rats fed SPI compared with rats fed CAS even though CYP3A1 mRNA and CYP3A apoprotein were significantly elevated. These data demonstrate that exposure to SPI during early development can increase CYP3A expression via post-transcriptional mechanisms and suggest that early soy consumption has potential effects on the metabolism of a wide variety of CYP3A substrates.