Evaluation of the modulatory role of nimodipine in mesentreric ischaemia/reperfusion-induced intestinal and vascular damage effect of stobadine

Abstract

This study examined the effects of the pyridoindole compound stobadine on intestinal and vascular injury following mesenteric ischemia/reperfusion (I/R) in rats. Ischemia was induced by occlusion of the superior mesenteric artery (SMA) for 60 min, followed by 30 min reperfusion. To characterize gut impairment, some parameters of intestinal damage and biochemical variables, such as GSH content, activity of a lysosomal enzyme N-acetyl-beta-D-glucuronidase and activity of gamma-glutamyl transpeptidase, were determined. Vascular I/R-induced damage was evaluated as changes in acetylcholine evoked relaxation of mesenteric artery rings under isometric conditions. A method of amplified chemiluminescence (CL) was used to detect production of reactive oxygen species (ROS). Following I/R, pronounced intestinal injury of various intensities was observed, with maximal changes occurring in the terminal ileum. The effect of I/R was expressed mainly as increased vascular permeability, with protein leakage and subsequent hemorrhagic injury of the intestine as well as impaired endothelium-dependent SMA relaxation. Vessel dysfunction was manifested by a decrease of the maximal relaxation response to acetylcholine. An increase of CL, indicative of increased ROS production, was observed in both intestinal and vascular tissue. A novel antioxidant, stobadine, was found to reduce the increased vascular permeability and the extent of small intestine injury caused by I/R, to improve biochemical alterations accompanying I/R, to protect endothelial-dependent relaxation of mesenteric arteries, and to attenuate the CL response. The observed beneficial effect of stobadine indicates its possible application in the preventive and/or therapeutic approach to I/R-induced pathologies.