Induction of cytochrome P450 1A by cow milk-based formula: A comparative study between human milk and formula

Haibo Xu, Ratheishan Rajesan, Patricia Harper, Richard B. Kim, Bo Lonnerdal, Mingdong Yang, Satoko Uematsu, Janine Hutson, Jo Watson-MacDonell, Shinya Ito

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

During the treatment of neonatal apnea, formula-fed infants, compared to breastfed infants, show nearly three-fold increase in clearance of caffeine, a substrate of cytochrome P450 1A (CYP1A) and in part CYP3A4. However, human milk is known to contain higher concentrations of environmental pollutants than infant formula, which are potent CYP1A inducers. To gain insight into the mechanism underlying this apparent contradiction, we characterized CYP1A and CYP3A4 induction by human milk and cow milk-based infant formula. The mRNA and protein expression of CYP1A1/1A2 were significantly induced by cow milk-based formula, but not by human milk, in HepG2 cells. Luciferase reporter assay demonstrated that cow milk-based formula but not human milk activated aryl hydrocarbon receptor (AhR) significantly. The cotreatment of 3,4-dimethoxyflavone, an AhR antagonist, abolished the formula-induced CYP1A expression. In addition, AhR activation by dibenzo[a,h]anthracene, a potent AhR agonist, was significantly suppressed by infant formula and even more by human milk. In contrast, CYP3A4 mRNA expression was only mildly induced by formula and human milk. Consistently, neither formula nor human milk substantially activated pregnane X receptor (PXR). Effects of whey and soy protein-based formulas on the AhR-CYP1A and the PXR-CYP3A4 pathways were similar to those of cow milk-based formula. In conclusion, infant formula, but not human milk, enhances in vitro CYP1A expression via an AhR-mediated pathway, providing a potential mechanistic basis for the increased caffeine elimination in formula-fed infants.

Original languageEnglish (US)
Pages (from-to)296-305
Number of pages10
JournalBritish Journal of Pharmacology
Volume146
Issue number2
DOIs
StatePublished - 2005

Fingerprint

Human Milk
Aryl Hydrocarbon Receptors
Cytochrome P-450 Enzyme System
Infant Formula
Milk
Cytochrome P-450 CYP3A
Caffeine
Environmental Pollutants
Messenger RNA
Cytochrome P-450 CYP1A1
Soybean Proteins
Hep G2 Cells
Apnea
Luciferases

Keywords

  • Aryl hydrocarbon receptor
  • Cytochrome P450 1A
  • Cytochrome P450 3A4
  • Human milk
  • Infant formula
  • Pregnane X receptor

ASJC Scopus subject areas

  • Pharmacology

Cite this

Induction of cytochrome P450 1A by cow milk-based formula : A comparative study between human milk and formula. / Xu, Haibo; Rajesan, Ratheishan; Harper, Patricia; Kim, Richard B.; Lonnerdal, Bo; Yang, Mingdong; Uematsu, Satoko; Hutson, Janine; Watson-MacDonell, Jo; Ito, Shinya.

In: British Journal of Pharmacology, Vol. 146, No. 2, 2005, p. 296-305.

Research output: Contribution to journalArticle

Xu, H, Rajesan, R, Harper, P, Kim, RB, Lonnerdal, B, Yang, M, Uematsu, S, Hutson, J, Watson-MacDonell, J & Ito, S 2005, 'Induction of cytochrome P450 1A by cow milk-based formula: A comparative study between human milk and formula', British Journal of Pharmacology, vol. 146, no. 2, pp. 296-305. https://doi.org/10.1038/sj.bjp.0706319
Xu, Haibo ; Rajesan, Ratheishan ; Harper, Patricia ; Kim, Richard B. ; Lonnerdal, Bo ; Yang, Mingdong ; Uematsu, Satoko ; Hutson, Janine ; Watson-MacDonell, Jo ; Ito, Shinya. / Induction of cytochrome P450 1A by cow milk-based formula : A comparative study between human milk and formula. In: British Journal of Pharmacology. 2005 ; Vol. 146, No. 2. pp. 296-305.
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