The Effects of Apelin on Mesenteric Ischemia and Reperfusion Damage in an Experimental Rat Mode

Abstract

Objective: Intestinal ischemia-reperfusion (I/R) injury is associated with high morbidity and mortality rates. There is ongoing research to find an effective preventive or treatment agent. We aimed to evaluate the effects of apelin 13 (AP) on intestinal I/R injury in a rat model. Material and Methods:Twenty-four male Sprague-Dawley rats aged 6-8 weeks and weighing 280±20 g were equally divided into three groups (control, I/R and I/R+AP). The control group underwent superior mesenteric artery (SMA) mobilization alone without any clamping. In the I/R and I/R+AP groups, an atraumatic microvascular bulldog clamp was placed across the SMA at its point of origin from the aorta. In the I/R+AP group, 2 µg/kg/d apelin was administered intraperitoneally. After 60 minutes of ischemia, relaparotomy was performed to remove the microvascular clamp on the SMA for 3 hours of reperfusion. After 3 hours, tissue samples were obtained for biochemical [malondialdehyde (MDA) and glutathione (GSH) levels] and histopathological analyses.Results: MDA levels were significantly higher in the I/R group compared to the control group. Although MDA levels were lower in the I/R+AP group compared tothe I/R group, the difference was not statistically significant. There was also no significant difference between the I/R+AP and I/R groups regarding GSH levels. The median histopathological grade was significantly lower in the I/R+AP group compared to the I/R group (p=0.001).Conclusion: Apelin appeared to have a positive effect on oxidative injury; this did not reach statistical significance. Thus, the role of apelin and associated findings in the initial treatment of intestinal ischemia needs further large-scale animal studies before human use.

Promoting effect of adipocytokine, apelin, on hepatic injury in caerulein-induced acute pancreatitis in rats

“…Moreover apelin behaves as CAT activator as documented previously by Foussal et al 44 Improvement of hepatic antioxidant, GSH, with decreased MDA, under apelin treatment has been recorded previously in vitro, 41 and in vivo, in mesenteric I/R induced hepatic injury. 45 Increased leukocyte infiltration in AP group compared to the control one observed in our study, is a multistep process, coordinated by specific adhesion molecules and a major characteristic of human and experimental pancreatitis, constituting a critical link in mediating tissue damage in AP. A fact is supported by reduced tissue injury in Cn-induced AP with neutrophils depletion.…”

Function and regulation of apelin/APJ system in digestive physiology and pathology

“…Recently, researchers have increasingly focussed on the effect of the apelin/APJ system on ischemia/reperfusion (I/R) injury (Chen, Wu, Li, & Chen, ; Y. Yang, Lv, Lyu, Wu, & Chen, ). The pathophysiology of I/R injury is extremely complex, including vascular endothelial cells, leukocytes, oxygen radicals, inflammatory mediators such as platelet‐activating factor and tumor necrosis factor, and adhesion molecules (Sagiroglu et al, ). Apelin could activate multiple protective mechanisms to prevent the heart, brain, liver, and kidney I/R injury (Y. Yang et al, ).…”

“…Irregular dilate arteries express higher levels of apelin. A signal for arteriogenesis in HCC(Muto et al, 2014) Treated with F13A Inhibit tumor growth, decrease arterioles I/R injury 24 male Sprague-Dawley rats I/R model MDA levels were significantly higher in the I/R group, MDA levels were lower in the I/ R+AP group(Sagiroglu et al, 2012) Note. AMPK: AMP-activated protein kinase; AS: acute stress; BMP2: bone morphogenetic protein-2; CD: Crohn's disease; CHeS: chronic heterotypic stress; CHS: chronic homotypic stress; CLD: chronic liver disease; CP: chronic pancreatitis; CRC: colorectal cancer; CRF: corticotropin-releasing factor; CRT: concurrent chemoradiotherapy; DSS: sodium dextran sulfate; EC: endothelial cell; ERK: extracellular signalregulated kinase; GI: gastrointestinal; GC: gastric cancer; HCC: hepatocellular carcinoma; HIF-1a: hypoxia inducible factor1a; HPC: hematopoietic progenitor cell ; HSC: hematopoietic stem cell ; hsCRP: high sensitive C-reactive protein; HVPG: hepatic venous pressure gradient; IEM: immunoelectron microscopy; IHC: immunohistochemistry; Il-10 -/-: Il-10 deficient; I/R: intestinal ischemia-reperfusion; JNK: c-Jun N-terminal kinase; J o2: an agonistic anti-Fas antibody (clone); LPS: lipopolysaccharide; LXR: liver X receptor; MAT: mesenteric adipose tissue; MAPK: mitogen-activated protein kinase; MDA: malondialdehyde ; MIP: macrophage inflammatory protein; MMP: matrix metalloproteinases; NAFLD: nonalcoholic fatty liver disease; PDL: pancreatic duct ligation; PDGFRβ: platelet-derived growth factor receptor β; PGE2: prostaglandin E2; PI3K: phosphatidylinositol-4,5bisphosphate 3 kinase; PPAR-α: peroxisome proliferator-activated receptor α; PTHrP: parathyroid hormone-related protein; s-apelin: serum apelin; SREBP-1c: sterol regulatory element-binding protein 1c; STAT3: signal transducer and activator of transcription 3; TIMP: tissue inhibitors of matrix metalloproteinase; TNF-α: tumor necrosis factorα; UC: ulcerative colitis; VEGF: vascular endothelial growth factor; WIRS: water-immersion and restraint stress; 4-HNE: the concentration of 4-hydroxynonenal.…”

Sesamin ameliorates mucosal tissue injury of mesenteric ischemia and reperfusion in an experimental rat model

“…Despite the fact that studies on mesenteric ischemia reperfusion injury treatment have been performed with many agents in the literature, no study on the effect of sesamin on mesenteric ischemia reperfusion injury has been seen [26–28]. In a study conducted by Torun et al ., it has been shown that TAS, TOS, and OSI values may not only be an indication of oxidative or antioxidative status but may also be used to evaluate treatment response [29, 30].…”