Effects of ulinastatin on renal ischemia-reperfusion injury in rats
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AIM: To investigate the effect and possible mechanism of ulinastatin on renal ischemia-reperfusion injury in rats. METHODS: Male Sprague-Dawley rats were subjected to 45-min bilateral renal ischemia, treated with intravenously 12 500 U ulinastatin at 30 min prior to ischemia and at the beginning of reperfusion, compared with a nontreated group without ulinastatin and a sham-operation group without bilateral renal ischemia. After 0 h, 2 h, 6 h, 12 h, and 24 h of reperfusion, serum creatinine and blood urea nitrogen were measured for the assessment of renal function, renal sections were used for histologic grading of renal injury, for immunohistochemical localization of Bcl-2 and heat shock protein 70. Renal ultrastructure was observed through a transmission electron microscope. RESULTS: Ulinastatin significantly reduced the increase in blood urea nitrogen and creatinine produced by renal ischemia-reperfusion, suggesting an improvement in renal function. Ulinastatin reduced the histologic evidence of renal damage associated with ischemia-reperfusion and accompanied with an up-regulation in the expression of Bcl-2 protein, but it had no significent effect on the expression of HSP 70. Ulinastatin also significantly reduced kidney ultrastructure damage caused by renal ischemia-reperfusion. CONCLUSION: The protease inhibitor, ulinastatin, reduced the renal dysfunction and injury associated with ischemia-reperfusion of the kidney. The protective effect of ulinastatin might be associated with the up-regulation of Bcl-2 expression and the effect on membrane fragility.Keywords:
Ulinastatin
Renal ischemia
Blood urea nitrogen
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Blood urea nitrogen
Renal ischemia
Intraperitoneal injection
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Background: Renal ischemia/reperfusion (I/R) injury, a common and important cause of acute kidney injury (AKI), is considered a major socioeconomic health problem.Stress, a state of disrupted normal homeostasis is known to trigger the progression of many illnesses.Objectives: This study was designed to determine changes in renal function and structure induced by renal I/R in rats subjected to chronic immobilization stress and to elucidate the possible underlying mechanism(s). Materials and Methods:Forty seven adult male albino rats were allocated into 3 groups: Group I: Sham-Operated Control, Group II: Renal I/R in which rats were subjected to 45 minutes ischemia followed by 24 hours of reperfusion, and Group III: Stressed Renal I/R in which rats were separately subjected to immobilization stress, 2 hours/day for 4 weeks, and then exposed to renal I/R procedure.All rats were subjected to determination of body weight (BW) and kidney weight (KW), plasma levels of creatinine, urea and tumor necrosis factor-α (TNF-α), as well as renal tissue levels of malondialdehyde (MDA), nitrite and catalase activity.Kidney tissues were also examined histopathologically.Results: Stressed renal I/R group showed significant decrease in final BW, BW % change, KW and KW/BW, and significant increase in plasma levels of creatinine, urea, TNF-α, renal tissue MDA, and nitrite levels as compared to both renal I/R and sham-operated groups.Renal catalase significantly increased as compared to renal I/R group, but significantly decreased compared to sham-operated group.Stress provoked significant augmentation in renal histomorphological damage scores compared to renal I/R and sham groups, evidenced in the form of glomerular capsular thickening and tuft retraction, tubular cells necrosis with loss of brush borders and cast formation, interstitial cell necrosis and hemorrhage, and endothelial cell disruption. Conclusion:Chronic immobilization stress aggravated renal dysfunction and morphological disturbance induced by renal I /R injury.Accentuation of oxidative stress, inflammation and nitric oxide may contribute to such effect.
Renal ischemia
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Malondialdehyde
Renal ischemia
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Objectives To investigate protective effect of recombinant human erythropeietin (rhEPO) on acute renal ischemia-reperfusion injury(IR/I) in rats.Methods Twenty one male S-D rats were randomly divided into 3 groups:Sham,IR/I,rhEPO(injection via intraperitoneal 2 h before surgery at the dosages of 1000U/kg).Rat model of renal IR/I was established with clamping both pedicles for 45 min followed by reperfusion.Blood sample and kidneys were collected at indicated times.Serum creatinine levels,urea nitrogen,histological change and mortality were observed throughout the study.ELISA was used to measure the levels of serum vascular endothelial growth factor(VEGF).The expression of heme oxygenase-1 (HO-1) in kidney observed by Immunohistochemical.Results Extensive proximal tubular necrosis,functional impairment and higher mortality were found repeffusion after 24 hours in IR/I group (P ＜ 0.01).Elevated serum VEGF levels and increased expression of HO-1 protein in kidney were significantly higher than IR/I group and sham group(P ＜ 0.01).Conclusions thEPO can attenuate renal IR/I.The protection mechanisms may be through the anti-oxidation and to promote renal tubular epithelial cell regeneration.
Key words:
Reperfusion Injury; Kidney; failure ; Rats; Erythropoietion, Recombinant
Blood urea nitrogen
Renal ischemia
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Objective To investigate the pathogenesis of hepatic ischemic-reperfusion (I/R) injury and observe the protection of ulinastatin on the liver. Methods Thirty-eight patients with hepatorrhexis undertaken hepatic hilum occlusion were selected. All patients were randomly divided into I/R group and ulinastatin group. Serum levels of tumor necrosis factor (TNF),malondialdehyde (MDA),aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were tested. The hepatic morphological changes were observed and the number of infiltrated neutrophil in liver tissue at 60 minutes of reperfusion was counted. Results Serum levels of TNF,MDA,AST and ALT in the I/R group were significantly higher than those in the ulinastatin group. Under light microscopy, neutrophils infiltration of liver tissue increased significantly, and electronic microscopic revealed that the hepatic sinusoidal endothelial cells and the hepatocellular mitochondria were injured in the I/R group. Pre_treatment with ulinastatin was able to significantly improved the pathological changes and decreased the hepatic I/R injury. Conclusion Hepatic I/R induce to release TNF-α,liver tissue is protected effectively from I/R injury by the ulinastatin pre_treatment.
Ulinastatin
Malondialdehyde
Pathogenesis
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Nitrotyrosine
Renal ischemia
Malondialdehyde
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Renal ischemia
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Blood urea nitrogen
Renal ischemia
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Objective: Here we investigate the effects of the endogenous prostaglandin D2 metabolite 15-deoxy-Δ12,14-prostaglandin J2, on the renal dysfunction and injury caused by ischemia/reperfusion of the kidney. Methods: Male Wistar rats, subjected to bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h, were administered 15-deoxy-Δ12,14-prostaglandin J2 (1 mg/kg, intravenously) 5 min prior to and again after 3 or 12 h reperfusion. Results: 15-deoxy-Δ12,14-prostaglandin J2 significantly reduced (i) renal and tubular dysfunction (serum urea and creatinine levels, creatinine clearance, fractional excretion of Na+ (FENa)), (ii) tubular and reperfusion-injury (urinary N-acetyl-β-d-glucosaminidase, aspartate aminotransferase (ASP) and γ-glutamyltransferase (γ-GT)) and (iii) histological evidence of renal injury. 15-deoxy-Δ12,14-prostaglandin J2 also improved renal function (plasma creatinine levels) and reduced the histological signs of renal injury (after 48 h reperfusion). Administration of 15-deoxy-Δ12,14-prostaglandin J2 markedly reduced the expression of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 during reperfusion (determined using immunohistochemistry). Immunohistochemical analysis of p65 translocation and Western blot analysis of IκB-α degradation revealed that 15-deoxy-Δ12,14-prostaglandin J2 inhibited the activation of nuclear factor (NF)-κB in renal cells. Subsequently, 15d-PGJ2 was able to significantly reduce nitric oxide production during renal ischemia/reperfusion and by primary cultures of rat proximal tubular (PT) cells incubated with interferon-γ and bacterial lipopolysaccharide (LPS) in combination. Conclusions: We demonstrate here, for the first time, that 15-deoxy-Δ12,14-prostaglandin J2 significantly reduces renal ischemia/reperfusion-injury via reduction of pro-inflammatory gene expression during reperfusion subsequent to the inhibition of the activation of NF-κB.
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To study the role of a protease inhibitor (ulinastatin) in protection of lung damage following hepatic ischemia/reperfusion in rat.Thirty-two healthy male SD rats were randomly divided into four groups (n=8 in each group). Group A was served as sham-injury control group, group B rats were subjected to 90 minutes hepatic ischemia, and group C rats underwent 120 minutes reperfusion after 90 minutes ischemia of the liver. Ulinastatin (UTI) was administered to animals in group D which were reperfused 120 minutes after 90 minutes of ischemia of the liver. In addition to plasma malondialdehyde (MDA), broncho-alveolar lavage fluid protein (BALFP) content, and lung dry-to-wet weight ratios (D/W) were respectively examined in each group. The concentration of myeloperoxidase (MPO) in lung tissue was also measured.Compared to group A, plasma MDA, content of MPO in lung tissues and BALFP were significantly increased in both group B and group C, but they were much lower than those in group D. In addition, D/W was markedly decreased during hepatic ischemia and after 120 minutes reperfusion, while it was significantly increased in animals pretreated with UTI.Acute lung injury after hepatic ischemia and reperfusion is mainly induced by the oxidant stress, and neutrophil infiltration in the lung tissues is responsible for the damage under these conditions. Proteases inhibitors such as UTI might have antioxidation effects which attenuate lung injury induced by trauma to remote organs.
Ulinastatin
Malondialdehyde
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