Pharmacological preconditioning with erythropoietin reduces ischemia-reperfusion injury in the small intestine of rats

Sayan, Hale | Özaçmak, Veysel Haktan | Şen, Feyza | Çabuk, Mehmet | Atik-Yörük, Duygu | Akyıldız-İğdem, Ayşenur | Özaçmak, I. Diler

Article | 2009 | Life Sciences84 ( 11.Dec ) , pp.364 - 371

Aims: Considering the implications that arose from several recent experimental studies using recombinant human erythropoietin in rodents, erythropoietin has been regarded as a pharmacological preconditioning agent. The purpose of the present study was to evaluate whether erythropoietin has a preconditioning effect against ischemia and reperfusion injury in the small intestine of the rat. Main methods: Intestinal ischemia was induced in male Wistar rats by clamping the superior mesenteric artery for 30 min, followed by reperfusion for 180 min. Recombinant human erythropoietin (1000 or 3000 U/kg) or vehicle was administered intraperit . . .oneally 24 h prior to ischemia. After collection of ileal tissue, evaluation of damage was based on measurements of the accumulation of polymorphonuclear neutrophils by technetium-99m-labeled leukocyte uptake, content of malondialdehyde, reduced glutathione, contractile responses to agonists, and an evaluation of histopathological features in intestinal tissue. Key findings: Treatment with erythropoietin 24 h before ischemia significantly reduced the tissue content of malondialdehyde and increased that of reduced glutathione. Pretreatment also significantly suppressed leukocyte infiltration into the postischemic tissue, as evidenced by the lower content of myeloperoxidase and technetium-99m-labeled leukocytes. Physiological and histopathological improvements were also significant with the rHuEpo treatment. Significance: Results of the present study indicate that rHuEpo is an effective preconditioning agent in ischemic injury of the small intestine. Protection provided by recombinant human erythropoietin is closely related to the inhibition of oxidative stress and leukocyte infiltration, which might be among the possible protective mechanisms of erythropoietin in intestinal ischemia and reperfusion. © 2009 Elsevier Inc. All rights reserved Daha fazlası Daha az

Protective effect of melatonin on contractile activity and oxidative injury induced by ischemia and reperfusion of rat ileum

Özaçmak, Veysel Haktan | Sayan, Hale | Arslan, S. Oktay | Altaner, Şemsi | Aktaş, R.Gülhan

Article | 2005 | Life Sciences76 ( 14 ) , pp.1575 - 1588

Free radicals derived from molecular oxygen have been reported to be responsible for changes in motility and mucosal damage observed in intestinal ischemia-reperfusion injury. Melatonin has been considered as an antioxidant that prevents injuries resulted from I/R in various tissues. The present study was designed to determine the effect of melatonin on the contractile responses of acetylcholine (Ach) and KCl, on malondialdehyde (MDA), a product of lipid peroxidation, and reduced glutathione (GSH) levels and to assess histopathological changes in the smooth muscle of terminal ileum subjected to ischemia-reperfusion. The intestinal i . . .schemia-reperfusion was induced by occlusion of superior mesenteric artery of rat for 30 min, followed by a period of reperfusion for 3 h. Melatonin at doses of 10 or 50 mg/kg was administered via the tail vein in 5 min prior to reperfusion. Following reperfusion, segments of terminal ileum were rapidly taken and transferred into isolated organ bath and responses to Ach and KCl were recorded. Samples of terminal ileum were also taken for measuring the MDA and GSH levels. EC50 values of these contracting substances were seriously reduced in the ischemia-reperfusion group compared to that of the sham-operated control group. The decreased contraction response to Ach and KCl was significantly ameliorated by a dosage of 50 mg/kg of melatonin, while not by a dosage of 10 mg/kg. Similar pattern of the effect was observed in the tissue levels of MDA and GSH as well as in histological improvement. Melatonin appeared to be restoring the amounts of tissue MDA and GSH back to about control levels. These results suggest that the high dose of melatonin not only physiologically but also biochemically and morphologically could be useful to normalize contractility injured by oxidative stress in intestinal ischemia-reperfusion. © 2004 Elsevier Inc. All rights reserved Daha fazlası Daha az

Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats

Turan, İnci | Özaçmak-Sayan, Hale | Özaçmak, Veysel Haktan | Barut, Figen | Araslı, Mehmet

Article | 2017 | Life Sciences189 , pp.23 - 28

Aims Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. Main methods Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10 mg/kg) was administer . . .ed intraperitoneally before reperfusion period. After 180 min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. Key findings The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-?, and IL-1? were brought back to the sham control levels by the treatment as well. Significance Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress. © 2017 Elsevier Inc Daha fazlası Daha az

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