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Acute mesenteric ischemia (AMI) is caused by an abrupt cessation of blood flow to the small intestine. Reperfusion is the return of blood flow to the ischemic bowel. Intestinal ischemia/reperfusion (I/R) leads to the formation of reactive oxygen species, local inflammatory response, and may lead to the patient's death. Pre-treatment of the intestinal may reduce the high mortality associated with AMI. 5-Hydroxytryptamine 1B (5-HT1B) and 5-HT1D receptors have anti-inflammatory and neuroprotective effects in different experimental studies. We aimed to investigate the potential involvement of these receptors in intestinal I/R injury. Firstly, we assessed the expression and localization of 5-HT1B and 5-HT1D receptors in the enteric nervous system using an immunofluorescence-based method. Intestinal I/R in rats was induced by 30 min occlusion of superior mesenteric artery and reperfusion for 2 h. Rats were randomly divided in different control and I/R groups (n = 6) receiving either vehicle, sumatriptan (5-HT1B/1D receptors agonist; 0.1 mg/kg), GR127,935 (5-HT1B/1D receptors antagonist; 0.1 mg/kg) and combination of sumatriptan (0.1 mg/kg) + GR127,935 (0.1 mg/kg) before determination of biochemical and histological parameters. In the enteric nervous system, 5-HT1B and 5-HT1D receptors were expressed 17% and 11.5%, respectively. Pre-treatment with sumatriptan decreased 5-hydroxytryptamine (5HT) level by 53%, and significantly decreased calcitonin gene-related peptide (CGRP) levels, lipid pereoxidation, neutrophil infiltration, and level of pro-inflammatory markers in the serum. Histopathologic studies also showed a remarkable decrease in intestinal tissue injury. These findings suggest that sumatriptan may inhibit intestinal injury induced by I/R through modulating the inflammatory response by activation of 5-HT1B/1D receptors. Copyright © 2020 Elsevier B.V. All rights reserved.


Fatemeh Gharishvandi, Alireza Abdollahi, Hamed Shafaroodi, Razieh Mohammad Jafari, Parvin Pasalar, Ahmad Reza Dehpour. Involvement of 5-HT1B/1D receptors in the inflammatory response and oxidative stress in intestinal ischemia/reperfusion in rats. European journal of pharmacology. 2020 Sep 05;882:173265

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PMID: 32574671

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