estradiol-3-benzoate and Colitis

Bisphenol A (BPA), a chemical estrogen widely used in the food-packaging industry and baby bottles, is recovered in human fluids (0.1-10 nM). Recent studies have reported that BPA is hormonally active at low doses, emphasizing the debate of a risk for human health. Estrogen receptors are expressed in the colon, and although the major route of BPA exposure is food, the effects on gut have received no attention. We first examined the endocrine disrupting potency of BPA on colonic paracellular permeability (CPP), experimental colitis, and visceral sensitivity in ovariectomized rats orally exposed to 5 mg/kg/d BPA (i.e., the no observed adverse effect level), 50 microg/kg/d BPA (i.e., tolerable daily intake), or lower doses. BPA dose-dependently decreased basal CPP, with a half-maximal inhibitory dose of 5.2 microg/kg/d, 10-fold below the tolerable daily intake. This correlated with an increase in epithelial tight junction sealing, also observed in Caco-2 cells exposed to 10 nM BPA. When ovariectomized rats were fed with BPA at the no observed adverse effect level, the severity of colitis was reduced, whereas the same dose increased pain sensitivity to colorectal stimuli. We then examined the impact of perinatal exposure to BPA on intestinal permeability and inflammatory response in the offspring. In female rats, but not in male rats, perinatal BPA evoked a decrease of CPP in adulthood, whereas the proinflammatory response of colonic mucosa was strengthened. This study first demonstrates that the xenoestrogen BPA at reference doses influences intestinal barrier function and gut nociception. Moreover, perinatal exposure promotes the development of severe inflammation in adult female offspring only.

Topics: Administration, Oral; Animals; Benzhydryl Compounds; Caco-2 Cells; Cell Adhesion Molecules; Colitis; Colon; Dose-Response Relationship, Drug; Estradiol; Estrogens, Non-Steroidal; Female; Humans; Inflammation; Intestinal Absorption; Male; Membrane Proteins; No-Observed-Adverse-Effect Level; Occludin; Ovariectomy; Permeability; Phenols; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Receptors, Estrogen; Sex Factors; Tight Junctions

Sex steroids influence IBD symptoms. Macrophage migration inhibitory factor (MIF), a target of sex steroids in other inflammatory models, promotes interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha release in colitis. We investigated whether estradiol and progesterone influence MIF, IL-1beta, and TNF-alpha production in experimental colitis.. Colonic MIF, IL-1beta, and TNF-alpha levels were measured in cyclic and ovariectomized rats, with or without estradiol benzoate (EB) or progesterone (P) replacement. MIF distribution was assessed by immunohistochemistry. Cytokines, myeloperoxidase activity, macroscopic damage, and plasma corticosterone were assessed 24 hours after intrarectal trinitrobenzene sulfonic acid (TNBS), with and without neutralizing anti-MIF antibody. Effects of EB and P on myeloperoxidase activity and MIF concentration were also assessed at 7 days in dextran sulfate sodium-induced colitis.. Basal IL-1beta and TNF-alpha contents did not fluctuate during the estrous cycle, while MIF concentrations increased from estrus (estrogen dominance) to metestrus (P dominance; P < .05). EB and P treatment mimicked these effects in ovariectomized rats, and similarly altered MIF immunostaining. Progesterone dominance aggravated TNBS colitis in comparison with estrogen. Progesterone enhanced TNBS-induced MIF (P < .001) and TNF-alpha (P < .01) production, while EB decreased MIF (P < .01) and IL-beta levels (P < .01). Anti-MIF antibody prevented P-mediated up-regulation of TNF-alpha, improved TNBS colitis, and enhanced plasma corticosterone. At 7 days after dextran sulfate sodium, EB decreased myeloperoxidase activity and MIF concentration, while P had no effect.. Estrogen decreases while progesterone increases MIF production in the female rat colon. Changes in basal MIF contents may affect colon susceptibility to inflammation, by modulating TNF-alpha and IL-1beta production during early stages of colitis.

Topics: Animals; Antibodies, Monoclonal; Colitis; Colon; Corticosterone; Dextran Sulfate; Disease Models, Animal; Estradiol; Estrous Cycle; Female; Gonadal Steroid Hormones; Immunohistochemistry; Interleukin-1beta; Intramolecular Oxidoreductases; Macrophage Migration-Inhibitory Factors; Ovariectomy; Peroxidase; Progesterone; Rats; Rats, Wistar; Severity of Illness Index; Sex Factors; Time Factors; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha

To evaluate the role of estrogen treatment on the healing of acetic acid-induced gastric or colonic injury, rats were given 17beta estradiol benzoate (0.001, 0.1, and 10 mg/kg) or vehicle for 7 days (following the induction of ulcer) or 4 days (following the induction of colitis) until they were decapitated. Food intake and fecal output were decreased by estradiol treatment but gastric emptying rate was not changed. Estradiol (10 mg/kg) reduced gastric ulcer index and colonic damage score compared to vehicle-treated groups. SEM and light microscopy demonstrated a significant reduction in the severity of ulcers and colitis by estradiol treatment. Gastric microscopic score was not changed by estradiol treatment, whereas in the colonic tissue score was significantly reduced. Elevated gastric MPO levels were reduced in gastric but not in colonic tissues as compared with corresponding vehicle groups. In conclusion, exogenous estradiol treatment at pharmacological doses improves the healing of both gastric and colonic injury induced by acetic acid in rats.

Topics: Acetic Acid; Animals; Colitis; Dose-Response Relationship, Drug; Epithelium; Estradiol; Female; Male; Microscopy, Electron; Rats; Rats, Inbred Strains; Severity of Illness Index; Stomach Ulcer; Treatment Outcome