Application of vascular endothelial growth factor at different phases of intestinal ischemia/reperfusion: what are its effects on oxidative stress, inflammation and telomerase activity?

Background. Intestinal ischemic reperfusion injury (IRI) represents a great challenge in clinical practice, with high morbidity and mortality. Vascular endothelial growth factor (VEGF), asasignal protein, contributes tovasculogenesis and angiogenesis.Objectives. To evaluate the local effectiveness of VEGF following intestinal IRI and its relation with application time.Material and methods. Thirty Wistar albino rats were allocated to5 groups and underwent laparotomy. Thesuperior mesenteric arteries (SMA) were dissected in4 groups, while thecontrol group (GrC) underwent aresection ofsmall and large intestines. The VEGF group (Gr V) received VEGF following SMA dissection, with no further intervention, and theremaining 3 groups were subjected toischemia for 90min through occlusion ofSMA and reperfusion for 4h. Ischemic reperfusion group (Gr I/R) received no additional medication, while theremaining 2 groups received VEGF just before ischemia (Gr V+I/R) and during reperfusion (Gr I/R+V).Results. Both applications of VEGF caused decreases inplasma levels of interleukin6 (IL-6), tumor necrosis factor ? (TNF-?), intestinal malondialdehyde (MDA), oxidized glutathione, protein carbonyl levels, and increases inintestinal total glutathione and superoxide dismutase (SOD) levels. Telomerase activity, which disappeared for Gr I/R, was found to be elevated following both treatment groups. Similarly, the histopathological scores were found better for both treatment groups, but Gr V-I/R represented best outcomes.Conclusions. The findings of our study revealed that VEGF, applied either before ischemia or during reperfusion, iseffective onlocal damage following intestinal IRI. Byinterpreting thebiochemical analysis and histopathological findings, we conclude either treatment option to be considered according to the reason of intestinal IRI

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

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