phytoestrogens and Acute-Disease

Dietary guidance recommends consumption of whole grains to reduce the risk of chronic diseases including cancer and cardiovascular disease. Epidemiologic studies support the belief that whole grains are protective against cancers, especially gastrointestinal cancers such as gastric and colonic, and cardiovascular disease. Components in whole grains that may be protective are diverse and include compounds that affect the gut environment, i.e., dietary fiber, resistant starch, and other undigestible compounds in whole grains, compounds that function as antioxidants such as trace minerals and phenolic compounds, and compounds that are phytoestrogens with potential hormonal effects. Many of the protective compounds in whole grains are also in fruits and vegetables, but some plant compounds are more concentrated in whole grains, such as phenolic compounds including ferulic and caffeic acid. Other potential mechanistic effects of whole grains include binding of carcinogens and modulation of glycemic index. Clearly, the range of protective substances in whole grains is impressive, and advice to consume additional whole grains is justifiable.

Topics: Acute Disease; Antioxidants; Cardiovascular Diseases; Dietary Fiber; Eating; Edible Grain; Estrogens, Non-Steroidal; Humans; Intestine, Large; Isoflavones; Lignans; Models, Biological; Neoplasms; Nutritional Requirements; Phytoestrogens; Plant Preparations; Risk Factors; Starch

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 microg/g feed; daidzein: 232 microg/g feed) or very low levels (genistein and daidzein <10 microg/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.

Topics: Acute Disease; Animal Feed; Animals; Colitis; Colon; Cyclooxygenase 2; Diet; Disease Models, Animal; Female; Organ Size; Peroxidase; Phytoestrogens; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Trinitrobenzenesulfonic Acid; Uterus

Since the two estrogen receptor isoforms ERalpha and ERbeta have been discovered it is unclear by which receptor immunomodulating or feminizing effects are mediated. In this study, the effects of the two selective ERalpha- and ERbeta-agonists ethinylestradiol and biochaninA, respectively, on acute cardiac allograft rejection, uterus growth, vascular adhesion molecule and MHC-II expression were investigated and verified using in vitro cell culture.. Heterotopic Lewis to ovarectomized F344 cardiac transplantations were performed. The study groups received supplemental biochaninA or ethinylestradiol, the control group received no treatment. Grafts and uteri were harvested on the fifth postoperative day and blood was taken for hormone plasma level quantifications. Purified Lewis aortic endothelial cell cultures were pre-treated with biochaninA or ethinylestradiol and stimulated with TNF-alpha or IFN-gamma for quantification of ICAM-1/VCAM-1 and MHC-II expression. Endothelium-lymphocyte adhesion assays were performed using purified F344 lymphocytes.. Both biochaninA and ethinylestradiol treatment significantly reduced graft mononuclear infiltration of CD8(+) and ED1(+) cells and markedly reduced ISHLT grading compared to untreated controls. Either agent significantly inhibited lymphocyte adhesion, endothelial VCAM-1 upregulation during graft rejection and during TNF-alpha-stimulation in vitro, whereas no effect was observed for ICAM-1 upregulation. BiochaninA but not ethinylestradiol significantly reduced endothelial MHC-II upregulation in vivo and in vitro. Only ethinylestradiol treatment strongly affected uterus growth in ovarectomized recipients.. Only the treatment with the phytoestrogen biochaninA reduced endothelial MHC-II expression in vivo and in vitro and weakened allograft rejection without affecting the reproductive system. Supplemental phytoestrogens may therefore provide further benefits in the clinical setting.

Topics: Acute Disease; Animals; Cell Adhesion; Cell Adhesion Molecules; Endothelial Cells; Female; Genistein; Graft Rejection; Heart Transplantation; Histocompatibility Antigens Class II; Lymphocytes; Organ Size; Phytoestrogens; Rats; Rats, Inbred Lew; Receptors, Estrogen; Uterus