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Involvement of 5-Ht1b/1D Receptors in the Inflammatory Response and Oxidative Stress in Intestinal Ischemia/Reperfusion in Rats Publisher Pubmed



Gharishvandi F1 ; Abdollahi A2 ; Shafaroodi H3, 4 ; Mohammad Jafari R4 ; Pasalar P1 ; Dehpour AR3, 4, 5
Authors
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Authors Affiliations
  1. 1. Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Imam Hospital Complex, Tehran, Iran
  3. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Brain and Spinal Injury Repair Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: European Journal of Pharmacology Published:2020


Abstract

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. © 2020 Elsevier B.V.
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