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In utero and postnatal exposure to a phytoestrogen-enriched diet increases parameters of acute inflammation in a rat model of TNBS-induced colitis

  • Organ Toxicity and Mechanisms
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Abstract

Inflammatory bowel disease (IBD) is very common in Europe and USA. Its incidence in East Asia has been traditionally low, albeit the risk of IBD increases in Asian immigrants adopting western lifestyles, suggesting a strong role of environmental/dietary factors in IBD. A lifelong exposure to phytoestrogen-rich diets has been associated with a decreased risk of developing breast cancer and might also be protective against IBD. We studied the influence of in utero and postnatal exposure to a phytoestrogen (PE)-rich diet on acute inflammation in an animal model of TNBS-induced colitis. Wistar rats were exposed in utero and postnatally to high (genistein: 240 μg/g feed; daidzein: 232 μg/g feed) or very low levels (genistein and daidzein <10 μg/g feed) of phytoestrogen isoflavones fed to pregnant dams with the diet and throughout nursing. After weaning, the offspring had free access to these diets. At the age of 11 weeks, colitis was induced with an enema of TNBS. After 3 days, animals were sacrificed and tissues were collected for histological evaluation and analysis of molecular markers of inflammation. Animals kept on a PE-rich diet (PRD) had higher colon weights than animals on low PE-levels (PDD), suggesting enhanced acute inflammation by phytoestrogens. This result was supported by histological findings and by analysis of myeloperoxidase activity. Interestingly, relative mRNA and protein expression of cyclooxygenase-2 (COX-2) were modulated in rats on PRD, providing evidence that COX-2, the inducible isoform of the enzyme, is involved in the management of colonic inflammation. Our results suggest that early-in-life exposure to PE might not protect against the development of IBD but enhances the extent of acute inflammation.

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Abbreviations

b.w.:

Body weight

COX-2:

Cyclooxygenase-2

CT:

Threshold cycle

ER:

Estrogen receptor

ERβ:

Estrogen receptor beta

HETAB:

Hexadecyltrimethylammonium bromide

IBD:

Inflammatory bowel disease

IU:

International units

MPO:

Myeloperoxidase

OD:

Outer diameter

PDD:

Phytoestrogen-depleted diet

PE:

Phytoestrogen

PRD:

Phytoestrogen-rich diet

TMB:

Tetramethyl benzidine

TNBS:

2,4,6-Trinitrobenzenesulfonic acid

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Acknowledgments

This work was supported by DFG grant DI 716/10-3. The authors wish to thank Dr. Eric Houdeau of the Institut National de la Recherche Agronomique, Toulouse, France, for providing valuable background information, Dr. Natali Bauer of the University of Giessen, Germany, for the performance of blood counts, and Cathrin Häusser (DSHS) for technical assistance during this study.

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Authors and Affiliations

  1. Department of Molecular and Cellular Sports Medicine, DSHS Cologne, Am Sportpark Müngersdorf, 50933, Cologne, Germany

    Jan Seibel, Almut F. Molzberger, Torsten Hertrampf, Ute Laudenbach-Leschowski & Patrick Diel

  2. Institut für Arbeitsphysiologie an der Universität Dortmund, Leibniz Research Centre for Working Environment and Human Factors, Ardeystr. 67, 44139, Dortmund, Germany

    Gisela H. Degen

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  1. Jan Seibel
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  2. Almut F. Molzberger
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  5. Gisela H. Degen
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  6. Patrick Diel
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Correspondence to Patrick Diel.

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Seibel, J., Molzberger, A.F., Hertrampf, T. et al. In utero and postnatal exposure to a phytoestrogen-enriched diet increases parameters of acute inflammation in a rat model of TNBS-induced colitis. Arch Toxicol 82, 941–950 (2008). https://doi.org/10.1007/s00204-008-0309-7

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