Effects of vascular endothelial growth factor (vegf) on remote organs in an experimental model of intestinal ischemic reperfusion injury

Abstract

Ischemic reperfusion injury (IRI) is a dual process with local damage due to hypoxia during ischemia and additional local and systemic injury due to inflammation and oxidative damage during reperfusion. Vascular endothelial growth factor (VEGF) is a protein known to stimulate vasculogenesis and angiogenesis. It is also accepted to alleviate the effects of IRI as it has antioxidant and vasodilator properties. The aim of this study is to evaluate the remote organ effects of VEGF in an experimental model of mesenteric ischemia and reperfusion. After obtaining Animals Ethic Committee approval, 24 male Wistar Albino rats were assigned to 4 groups. All animals underwent a midline laparotomy and dissection of mesenteric artery. Sham group received no further intervention (Gr S, n = 6) and VEGF group received intravascular VEGF (0.8 mu g/kg) via caudal caval vein (Gr V, n = 6). The rest of the groups were subjected to 90 min of ischemia by occlusion of superior mesenteric artery and 4 h of reperfusion. Ischemic reperfusion injury group (Gr I/R, n = 6) received no additional medication while the other group received VEGF (0.8 mu g/kg) via caudal caval vein at the beginning of reperfusion period (Gr I/R+V, n = 6). At the end of reperfusion period, all rats were sacrificed and blood was sampled to evaluate hepatic and renal functions. Also the liver and kidney were harvested in order to evaluate malondialdehyde (MDA), glutathione (GSH), total nitrate/nitrite (NO x) levels and superoxide dismutase (SOD) and catalase (CAT) activities. The Kruskal-Wallis test and Mann-Whitney U-test with Bonferroni correction were used for statistical analysis. The administration of VEGF at the beginning of reperfusion caused decreases in MDA levels and SOD activities and increases in GSH levels and CAT activities for kidney and liver tissues when compared to ischemia reperfusion group. Similarly VEGF at the beginning of reperfusion enhanced renal functions. The remote organ effects of intestinal IRI can be prevented by VEGF as it presents antioxidant effects in addition to its angiogenesis promoter, and vasodilator effects

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