Etanercept Restores Vasocontractile Sensitivity Affected by Mesenteric Ischemia Reperfusion

Abstract

Background: The aim of the study is to evaluate in vivo and in vitro effects of etanercept, a soluble tumor necrosis factor receptor, on the contractile responses of superior mesenteric artery in an experimental mesenteric ischemia and reperfusion model.

Material and methods: After obtaining animal ethics committee approval, 24 Sprague eDawley rats were allocated to three groups. Control group (Gr C, n = 6) underwent a sham operation, whereas ischemia/reperfusion and treatment groups underwent 90 min ischemia and 24- h reperfusion (Gr I/R, n = 12; Gr I/RthornE, n = 6). The treatment group received 5 mg/kg etanercept intravenously at the beginning of reperfusion. At the end of reperfusion, all animals were sacrificed, and third branch of superior mesenteric artery was dissected for evaluation of contractile responses. In vitro effects of etanercept on vasocontractile responses were also evaluated. The excised ileums were analyzed under light microscope. Two- way analysis of variance following Bonferroni post hoc test was used for evaluation of contractile responses.

Results: Endothelin- 1 and phenylephrine- mediated vasocontractile sensitivity were found increased in Gr I/R when compared with Gr C. Both intravenous administration and organ bath incubation of etanercept decreased the sensitivity of contractile agents for Gr I/R. Mucosal injury, lamina propria disintegration, and denuded villous tips were observed in Gr I/R, whereas the epithelial injury and the subepithelial edema were found to be milder in Gr I/RthornE.

Conclusions: Etanercept can be a promising agent in mesenteric ischemic reperfusion injury as it does not only inhibit inflammation by blocking tumor necrosis factor- a in circulation but also restores vascular contractility during reflow. These findings support an unexplained recuperative effect of drug beyond its anti- inflammatory effects. (C) 2018 Elsevier Inc. All rights reserved.