Expression and Activity of CYP3A Enzymes in the Liver of Piglets Fed Dairy‐ or Soy‐Based Formula in Comparison to Breast Feeding

Abstract

We examined induction of CYP3A expression and activity in hepatic microsomes prepared from 21 d old male and female piglets either breast‐fed via the sow or fed dairy‐based or soy‐based formulas. Dairy formula‐feeding reduced CYP3A activity 20–40% (p < 0.05) compared to breast‐feeding. Soy‐formula increased CYP3A activities 2–3‐fold relative to diary‐formula fed piglets. These effects were more pronounced in females. A similar pattern of diet effects was observed on CYP3A protein expression measured in Western blots using antibodies raised against both rat CYP3A1 and human CYP3A4. Examination of expression patterns of mRNAs coded by the 4 known porcine CYP3A genes: CYP3A22, CYP3A29, CYP3A39 and CYP3A46 using quantitative RT‐PCR revealed increases in hepatic CYP3A29 mRNA in soy‐formula‐fed piglets of both sexes relative to dairy formula‐fed piglets and increases in CYP3A22 mRNA in soy‐formula fed females (p < 0.05). However, increases were only 15–20% suggesting diet effects on neonatal porcine CYP3A protein expression and activity are largely post‐transcriptional. No diet effects were observed on polyribosomal distribution of CYP3A29 mRNA, suggesting little effect on mRNA translation. These data suggest that formula feeding has significant effects on hepatic CYP3A activity and may alter clearance of pediatric medications relative to breast feeding. Supported in part by ARS CRIS #6251‐51000‐005‐00D.