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Oral treatment with genistein reduces the expression of molecular and biochemical markers of inflammation in a rat model of chronic TNBS-induced colitis

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Abstract

Background

Inflammatory bowel disease (IBD) in humans has a high incidence in Europe and the USA, whereas in East Asia, incidence has been historically low.

The risk of IBD appears to increase in Asian immigrants adopting western lifestyles, suggesting a strong link of environmental/dietary factors in the development of IBD. Exposure to high levels of isoflavones such as genistein (Gen) in traditional East Asian diets has been associated with a decreased risk of developing breast cancer and may also be beneficial for the prevention of IBD.

Aim

In this study, the effect of orally administered genistein on the inflammatory response in the TNBS-induced chronic colitis rat model was investigated.

Methods

Eighteen male Wistar rats, aged 12 weeks, were randomized to one of three groups (n = 6). Two groups received a 2,4,6-trinitrobenzenesulfonic acid (TNBS) enema, then were treated daily by oral gavage with either Gen (100 mg/kg b.w.) or vehicle, for 14 days. The last group served as a control group, not receiving the TNBS enema. At the end of the 14 days, animals were killed and tissues collected. Molecular and biochemical inflammatory markers in the colon, specifically cyclooxygenase-2 (COX-2) and myeloperoxidase (MPO), were analyzed. In addition, to assess the efficacy of Gen treatment, relative wet weights of the accessory sexual organs, specifically prostate and the seminal vesicle, were compared between the groups treated or not with Gen.

Results

Wet weights of both prostates and seminal vesicles were significantly (P < 0.01) reduced upon Gen administration. In the colon, expression of COX-2 mRNA and protein was reduced (P < 0.05) in the Gen treatment group, as compared to the control group, whereas there was no significant inhibitory effect of Gen on the expression of proliferating cell nuclear antigen. In Gen treated animals colon wet weight was not altered, however a decrease in MPO activity (P < 0.01) was seen.

Conclusion

These results may provide evidence that oral administration of Gen exerts beneficial anti-inflammatory effects in a rodent model of TNBS-induced chronic colitis. While the sample size of this study was small, it nevertheless might encourage the realization of larger blinded randomized controlled studies for the proof of concept.

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References

  1. Adlercreutz H (2002) Phytoestrogens and breast cancer. J Steroid Biochem Mol Biol 83:113–118

    Article  CAS  Google Scholar 

  2. Andoh A, Tsujikawa T, Ishizuka I, Araki Y, Sasaki M, Koyama S, Fujiyama Y (2003) N-3 fatty acid-rich diet prevents early response of interleukin-6 elevation in trinitrobenzene sulfonic acid-induced enteritis. Int J Mol Med 12:721–725

    CAS  Google Scholar 

  3. Arai Y, Uehara M, Sato Y, Kimira M, Eboshida A, Adlercreutz H, Watanabe S (2000) Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake. J Epidemiol 10:127–135

    CAS  Google Scholar 

  4. Bernstein CN, Blanchard JF, Kliewer E, Wajda A (2001) Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 91:854–862

    Article  CAS  Google Scholar 

  5. Blondel-Kucharski F, Chircop C, Marquis P, Cortot A, Baron F, Gendre JP, Colombel JF, Groupe d’Etudes Thérapeutique des Affections Inflammatoires Digestives (GETAID) (2001) Health-related quality of life in Crohn’s disease: a prospective longitudinal study in 231 patients. Am J Gastroenterol 96:2915–2920

    Article  CAS  Google Scholar 

  6. Davis SR, Dalais FS, Simpson ER, Murkies AL (1999) Phytoestrogens in health and disease. Recent Prog Horm Res 54:185–210 discussion 210–211

    CAS  Google Scholar 

  7. Garavito RM, Mulichak AM (2003) The structure of mammalian cyclooxygenases. Annu Rev Biophys Biomol Struct 32:183–206

    Article  CAS  Google Scholar 

  8. Grace PB, Taylor JI, Low YL, Luben RN, Mulligan AA, Botting NP, Dowsett M, Welch AA, Khaw KT, Wareham NJ, Day NE, Bingham SA (2004) Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary phytoestrogen intake and their relation to breast cancer risk in European prospective investigation of cancer and nutrition-norfolk. Cancer Epidemiol Biomarkers Prev 13:698–708

    CAS  Google Scholar 

  9. Grisham MB, Hernandez LA, Granger DN (1986) Xanthine oxidase and neutrophil infiltration in intestinal ischemia. Am J Physiol 251:G567–G574

    CAS  Google Scholar 

  10. Halfvarson J, Bodin L, Tysk C, Lindberg E, Jarnerot G (2003) Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. Gastroenterology 124:1767–1773

    Article  Google Scholar 

  11. Harnish DC, Albert LM, Leathurby Y, Eckert AM, Ciarletta A, Kasaian M, Keith JC Jr (2004) Beneficial effects of estrogen treatment in the HLA-B27 transgenic rat model of inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 286:G118–G125

    Article  CAS  Google Scholar 

  12. Harris HA, Albert LM, Leathurby Y, Malamas MS, Mewshaw RE, Miller CP, Kharode YP, Marzolf J, Komm BS, Winneker RC, Frail DE, Henderson RA, Zhu Y, Keith JC Jr (2003) Evaluation of an estrogen receptor-beta agonist in animal models of human disease. Endocrinology 144:4241–4249

    Article  CAS  Google Scholar 

  13. Hertrampf T, Schmidt S, Seibel J, Laudenbach-Leschowsky U, Degen GH, Diel P (2006) Effects of genistein on the mammary gland proliferation of adult ovariectomised Wistar rats. Planta Med 72:304–310

    Article  CAS  Google Scholar 

  14. Houdeau E, Larauche M, Monnerie R, Bueno L, Fioramonti J (2005) Uterine motor alterations and estrous cycle disturbances associated with colonic inflammation in the rat. Am J Physiol Regul Integr Comp Physiol 288:R630–R637

    CAS  Google Scholar 

  15. Jones MP, Wessinger S, Crowell MD (2006) Coping strategies and interpersonal support in patients with irritable bowel syndrome and inflammatory bowel disease. Clin Gastroenterol Hepatol 4:474–481

    Article  Google Scholar 

  16. Kerr SW, Wolyniec WW, Filipovic Z, Nodop SG, Braza F, Winquist RJ, Noonan TC (1999) Repeated measurement of intestinal permeability as an assessment of colitis severity in HLA-B27 transgenic rats. J Pharmacol Exp Ther 291:903–910

    CAS  Google Scholar 

  17. Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:863–870

    Article  CAS  Google Scholar 

  18. Lakatos PL (2006) Recent trends in the epidemiology of inflammatory bowel diseases: up or down? World J Gastroenterol 12:6102–6108

    Google Scholar 

  19. Linseisen J, Piller R, Hermann S, Chang-Claude J (2004) German case-control study. Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study. Int J Cancer 110:284–290

    Article  CAS  Google Scholar 

  20. Loftus EV Jr (2004) Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 126:1504–1517

    Article  Google Scholar 

  21. Martín AR, Villegas I, Sanchez-Hidalgo M, de la Lastra CA (2006) The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model. Br J Pharmacol 147:873–885

    Article  CAS  Google Scholar 

  22. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803

    CAS  Google Scholar 

  23. Nagata C, Takatsuka N, Inaba S, Kawakami N, Shimizu H (1998) Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women. J Natl Cancer Inst 90:1830–1835

    Article  CAS  Google Scholar 

  24. Nilsson S, Makela S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Warner M, Gustafsson JA (2001) Mechanisms of estrogen action. Physiol Rev 81:1535–1565

    CAS  Google Scholar 

  25. Radford-Smith GL, Edwards JE, Purdie DM, Pandeya N, Watson M, Martin NG, Green A, Newman B, Florin TH (2002) Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn’s disease. Gut 51:808–813

    Article  CAS  Google Scholar 

  26. Sadowska-Krowicka H, Mannick EE, Oliver PD, Sandoval M, Zhang XJ, Eloby-Childess S, Clark DA, Miller MJ (1998) Genistein and gut inflammation: role of nitric oxide. Proc Soc Exp Biol Med 217:351–357

    CAS  Google Scholar 

  27. Seibel J, Molzberger AF, Hertrampf T, Laudenbach-Leschowski U, Degen GH, Diel P (2008) 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

    Article  CAS  Google Scholar 

  28. Setchell KD (1998) Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 68:1333S–1346S

    CAS  Google Scholar 

  29. Smith WL, DeWitt DL, Garavito RM (2000) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69:145–182

    Article  CAS  Google Scholar 

  30. Subbaramaiah K, Dannenberg AJ (2003) Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol Sci 24:96–102

    Article  CAS  Google Scholar 

  31. Tobin MV, Logan RF, Langman MJ, McConnell RB, Gilmore IT (1987) Cigarette smoking and inflammatory bowel disease. Gastroenterology 93:316–321

    CAS  Google Scholar 

  32. Wu AH, Wan P, Hankin J, Tseng CC, Yu MC, Pike MC (2002) Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis 23:1491–1496

    Article  CAS  Google Scholar 

  33. Yamada T, Zimmerman BJ, Specian RD, Grisham MB (1991) Role of neutrophils in acetic acid-induced colitis in rats. Inflammation 15:399–411

    Article  CAS  Google Scholar 

  34. Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S (2003) Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst 95:906–913

    Article  CAS  Google Scholar 

  35. Yu AP, Cabanilla LA, Wu EQ, Mulani PM, Chao J (2008) The costs of Crohn’s disease in the United States and other Western countries: a systematic review. Curr Med Res Opin 24:319–328

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by DFG grant DI 716/10-3. The authors wish to thank Dr. Eric Houdeau (Institut National de la Recherche Agronomique, Toulouse, France) for providing valuable background information, Burkhardt Schleipen (German Sport University Cologne) for surgical assistance during this study and Martina Velders (German Sport University Cologne) and Dr. Lisa Rehm (Abbott Laboratories, Abbott Park, IL, USA) for careful and critical reading of the manuscript.

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Correspondence to Patrick Diel.

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Seibel, J., Molzberger, A.F., Hertrampf, T. et al. Oral treatment with genistein reduces the expression of molecular and biochemical markers of inflammation in a rat model of chronic TNBS-induced colitis. Eur J Nutr 48, 213–220 (2009). https://doi.org/10.1007/s00394-009-0004-3

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  • DOI: https://doi.org/10.1007/s00394-009-0004-3

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