نقش محافظتی استروژن و پروژسترون بر بافت معدی به دنبال ایسکمی- رپرفیوژن معدی در موش‌های صحرایی نر

Background and Objective: Ischemia-reperfusion (I/R) injury repeatedly occurs in situations such as surgery, hemorrhage, burns, trauma, and infection. It has also been found that females were more resistant than males, indicating that female sex hormones have a protective function. The aim of this study was to determine the role of estrogen, progesterone, and their combination in protecting the gastric damage induced by I/R. Materials and Methods: 40 Wistar rats were randomly divided into four groups: intact, ischemia - reperfusion (IR), IR + estradiol (1mg/kg), IR + progesterone (16 mg / kg) (P) and IR + combination of estradiol (1mg / kg) and progesterone (16 mg / kg). After animal anesthesia and laparotomy, celiac artery was occluded for 30 minutes and then circulation was established for 24 hours. Results expressed as mean ± SEM and P <0.05 was considered statistically significant. Results: The gastric acid concentration significantly increased after induction of gastric ischemia - reperfusion (p <0.001). Treatment with estradiol, progesterone (p <0.05) and combined estradiol and progesterone (p <0.01) significantly reduced gastric acid levels. The histopathological evaluation of gastric tissue indicated the presence of gastric ulcer with active bleeding, erosion, submucosal edema and identified inflammation in ischemia - reperfusion group. In groups treated with estrogen and progesterone, the ulcer was not found however, erosion, edema and inflammation of serous surfaces were observed. Conclusion: Regarding acid-lowering and protective effects of estrogen and progesterone upon gastric tissue following gastric ischemia-reperfusion, female sex steroids can be used to reduce gastrointestinal ischemic disorders. References 1- Dubin A, Estenssoro E, Murias G, et al. Effects of hemorrhage on gastrointestinal oxygenation. Intensive Care Med. 2001 27: 1931-6. 2- Qiao WL, Wang L, Zhang YM, Zhang JF, Wang GM. Extracellular signal-regulated kinase 1- and 2-mediated gastric mucosal injury and repair in gastric ischemia-reperfusion of rats. J Gastroenterol. 2006 41: 1158-66. 3- Sínay L, Kürthy M, Horváth S, et al. Ischemic postconditioning reduces peroxide formation, cytokine expression and leukocyte activation in reperfusion injury after abdominal aortic surgery in rat model. Clin Hemorheol Microcirc. 2008 40 133-42. 4- Wada K, Kamisaki Y, Kitano M, Kishimoto Y, Nakamoto K, Itoh T. A new gastric ulcer model induced by ischemia–reperfusion in the rat: role of leukocytes on ulceration in rat stomach. Life Sci. 1996 59: 295-301. 5- Herskowitz A, Choi S, Ansari AA, Wesselingh S. Cytokine mRNA expression in postischemic/ reperfusion myocardium. Am J Pathol. 1995 146: 419-28. 6- Andrews FJ, Malconenti-Wilson C, O’Brien PE. Polymorphonuclear leukocyte infiltration into gastric mucosa after ischemia-reperfusion. Am J Physiol. 1994 266: G48-G54. 7- Ishii M, Shimizu S, Nawata S, Kiuchi Y, Yamamoto T. Involvement of reactive oxygen species and nitric oxide in gastric ischemia reperfusion injury in rats: protective effect of tetrahydrobiopterin. Dig Dis Sci. 2000 45: 93-8. 8- Konturek PC, Duda A, Brzozowski T, et al. Activation of genes for superoxide dismutase, interleukin-1beta, tumor necrosis factor-alpha and intracellular adhesion molecule-1 during healing of ischemia reperfusion gastric injury. Scand J Gastroenterol. 2000 35: 425-63. 9- Brzozowski T, Konturek PC, Konturek SJ, Brzozowska I, Pawlik T. Role of prostaglandins in gastroprotection and gastric adaptation. J Physiol Pharmacol. 2005 56: 33-55. 10- Derin N, Izgut-Uysal VN, Agac A, Aliciguzel Y, Demir N. L-carnitine protects gastric mucosa by decreasing ischemia– reperfusion induced lipid peroxidation. J Physiol Pharmacol. 2004 55: 595-606. 11- Hiroshi H, Erik H, Da-Zhong X, Qi L, Rena F, Edwin A. The female intestine is more resistant than the male intestine to gut injury and inflammation when subjected to conditions associated with shock states. Am J Physiol Gastrointest Liver Physiol. 2005 288: G466-72. 12- Ueyama T, Shirasawa N, Numazawa M, et al. Gastric parietal cells: potent endocrine role in secreting estrogen as a possible regulator of gastro-hepatic axis. Endocrinology. 2002 143: 3162-70. 13- Saqui M, Rocha BL, Barrios JA, Ruiz G. Effects of estradiol and progesterone on gastric mucosal response to early Helicobacter pylori infection in female gerbils. Helicobacter. 2006 11: 123-30. 14- Feldman M, Richardson CT, Walsh JH. Sex-related differences in gastrin release and parietal cell sensitivity to gastrin in healthy human beings. J Clin Invest. 1983 71: 715-20. 15- Campbell-Thompson M, Reyher KK, Wilkinson LB. Immunolocalization of estrogen receptor α and β in gastricepithelium and enteric neurons. J Endocrinol. 2001 171: 65-73. 16- Smith A, Contreras C, Ko KH, et al. Gender-specific protection of estrogen against gastric acid-induced duodenal injury: stimulation of duodenal mucosal bicarbonate secretion. Endocrinology .2008 149: 4554-66. 17- Chen G, Shi J, Ding Y, Yin H, Hang C. Progesterone prevents traumatic brain injury-induced intestinal nuclear factor kappa B activation and proinflammatory cytokines expression in male rats. Mediators Inflamm. 2007 10: 1155-62. 18- Gemici B, Tan R, Ongüt G, Izgüt-Uysal VN. Expressions of inducible nitric oxide synthase and cyclooxygenase-2 in gastric ischemia-reperfusion: role of angiotensin II. J Surg Res. 2010 1 161: 126-33. 19- Girma K, Janczewska I, Romell B, Seensalu R, Sandin A, Wilander E, Nilsson G. Twenty-four-hour basal and repetitive pentagastrin stimulated gastric acid secretion in normal and sham-operated rats and in rats after gonadectomy or treatment with estradiol or testosterone. Scand J Gastroenterol. 1997 32: 669-75. 20- Patten RD, Pourati I, Aronovitz MJ, et al. 17betaestradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling. Circ Res. 2004 95: 692-99. 21- Satake A, Takaoka M, Nishikawa M, et al. Protective effect of 17β-estradiol on ischemic acute renal failure through the PI3K/Akt/eNOS pathway. Kidney Int. 2008 73: 308-17. 22- Fujita K, Kato T, Shibayama K, et al. Protective effect against 17β-estradiol on neuronal apoptosis in hippocampus tissue following transient ischemia/recirculation in Mongolian gerbils via down-regulation of tissue transglutaminase activity. Neurochem Res. 2006 31: 1059-68. 23- Montoneri C, Drago F. Effects of pregnancy in rats on cysteamine-induced peptic ulcers: role of progesterone. Dig Dis Sci. 1997 42: 2572-5. 24- Drago F, Montoneri C, Varga C, Laszlo F. Dual effect of female sex steroids on drug-induced gastroduodenal ulcers in the rat. Life Sci. 1999 25: 2341-50. 25- Machowska A, Szlachcic A, Pawlik M, Brzozowski T, Konturek SJ, Pawlik WW. The role of female and male sex hormones in the healing process of preexisting lingual and gastric ulcerations. J Physiol Pharmacol. 2004 55: 91-104. 26- Peluso JJ. Multiplicity of progesterone's actions and receptors in the mammalian ovary. Biol Reprod. 2006 75: 2-8. 27- Yamashita S. Localization and functions of steroid hormone receptors. Histol Histopathol. 1998 13: 255-270. 28- Saqui-Salces M, Neri-Gómez T, Gamboa- Dominguez A, Ruiz-Palacios G, Camacho-Arroyo I. Estrogen and progesterone receptor isoforms expression in the stomach of Mongolian gerbils. World J Gastroenterol. 2008 14: 5701-6. 29- Prokai-Tatrai K, Perjesi P, Rivera-Portalatin NM, Simpkins JW, Prokai L. Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative. Steroids. 2008 73: 280-8. 30- Kireev RA, Tresquerres AF, Vara E, Ariznavarreta C, Tresquerres JA. Effect of chronic treatments with GH, melatonin, estrogens, and phytoestrogens on oxidative stress parameters in liver from aged female rats. Bio-gerontology. 2007 8:469-82. 31- Liu MJ, Fei SJ, Qiao WL, et al. The protective effect of 17β-estradiol postconditioning against hypoxia/reoxygenation injury in human gastric epithelial cells. Eur J Pharmacol. 2010 645: 151-7. 32- Tuo B, Wen G, Wei J, Liu X, Wang X, Zhang Y, et al. Estrogen regulation of duodenal bicarbonate secretion and sex-specific protection of human duodenum. Gastroenterology. 2011 141: 854-63 33- Liu MJ, Fei SJ, Qiao WL, et al. The protective effect of 17β-estradiol postconditioning against hypoxia/reoxygenation injury in human gastric epithelial cells. Eur J Pharmacol. 2010 645: 151-7. 34- Ashokan K, Kurane M, Pillai M. Effect of ovariectomy and of estrogen administration upon duodenal ulceration induced by cysteamine. Internet J Gastroenterology. 2009 8. 35- Sangma TK, Jain S, Mediratta PK. Effect of ovarian sex hormones on non-steroidal anti-inflammatory drug-induced gastric lesions in female rats. Indian J Pharmacol. 2014 46: 113-6. 36- Drago F, Montoneri C, Varga C, Làszlò F. Dual effect of female sex steroids on drug-induced gastroduodenal ulcers in the rat. Life Sci. 1999 64: 2341-50.