5-Aminoisoquinolinone reduces renal injury and dysfunction caused by experimental ischemia/reperfusion

BACKGROUND: Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the development of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of a water-soluble and potent PARP inhibitor, 5-aminoisoquinolinone (5-AIQ), on the renal injury and dysfunction caused by oxidative stress of the rat kidney in vitro and in vivo. METHODS: Primary cultures of rat renal proximal tubular cells, subjected to oxidative stress caused by hydrogen peroxide (H2O2), were incubated with increasing concentrations of 5-AIQ (0.01 to 1 mmol/L) after which PARP activation, cellular injury, and cell death were measured. In in vivo experiments, anesthetized male Wistar rats were subjected to renal bilateral ischemia (45 minutes) followed by reperfusion (6 hours) in the absence or presence of 5-AIQ (0.3 mg/kg) after which renal dysfunction, injury and PARP activation were assessed. RESULTS: Incubation of proximal tubular cells with H2O2 caused a substantial increase in PARP activity, cellular injury, and cell death, which were all significantly reduced in a concentration-dependent by 5-AIQ [inhibitory concentration 50 (IC50) approximately 0.03 mmol/L]. In vivo, renal I/R resulted in renal dysfunction, injury, and PARP activation, primarily in the proximal tubules of the kidney. Administration of 5-AIQ significantly reduced the biochemical and histologic signs of renal dysfunction and injury and markedly reduced PARP activation caused by I/R. CONCLUSION: This study demonstrates that 5-AIQ is a potent, water soluble inhibitor of PARP activity, which can significantly reduce (1) cellular injury and death caused to primary cultures of rat proximal tubular cells by oxidative stress in vitro, and (2) renal injury and dysfunction caused by I/R of the kidney of the rat in vivo.     

Melatonin ameliorates renal ischemia/reperfusion injury

BACKGROUND: We studied whether melatonin is able to reduce organ damage during renal ischemia/reperfusion via its effects on the oxidative response in early and late reperfusion. MATERIALS AND METHODS: Renal ischemia/reperfusion injury (I/R) was induced in two groups of rats by 75 min occlusion of the left renal artery and vein and right nephrectomy, followed by reperfusion. The formation of reactive oxygen species was evaluated in the early reperfusion phase (60 min) by lipid peroxidation products and glutathione assay. In the late reperfusion phase (24 h) tissue neutrophil infiltration, inducible nitric oxide synthase (iNOS) gene expression, and histopathology were evaluated. Groups received either systemic melatonin (MEL) or normal saline (NS). There were two nonischemic sham control groups, one with and another without melatonin (S+MEL and S). RESULTS: Creatinine was higher in the NS group at all times. A reduction in glutathione and increases in lipid peroxidation products and myeloperoxidase activity induced by I/R indicated renal injury involving reactive oxygen formation. Melatonin reversed this oxidant response and reduced the rise in creatinine and iNOS expression. Seven-day group survivals were 5/10 for NS, 8/10 for MEL, and 10/10 for both Sham groups. CONCLUSIONS: Exogenous melatonin is able to preserve renal functional status following I/R-induced injury by increasing glutathione and reducing lipid peroxidation in the early reperfusion phase, without any apparent effect on neutrophil infiltration in the late reperfusion phase.     

Trimetazidine reduces renal dysfunction by limiting the cold ischemia/reperfusion injury in autotransplanted pig kidneys

Ischemia/reperfusion injury leads to delayed graft function, which is a major problem in kidney transplantation. This study investigated the effects of adding trimetazidine (TMZ) to the perfusate of cold-stored kidneys on the function of reperfused autotransplanted pig kidney. The left kidney was removed and cold-flushed with Euro-Collins (EC), or University of Wisconsin (UW) solutions with or without 10(-6)M TMZ and stored for 48 h at 4 degrees C. The kidneys were then autotransplanted and the contralateral kidneys were removed. Several parameters were analyzed over the 14 d after transplantation. The survival rate was 57% in pigs transplanted with kidneys cold-flushed with UW and 43% for those flushed with EC solution; it was 100% for pigs having kidneys cold-flushed with TMZ-supplemented UW and EC solutions. The functions of the transplanted kidneys were also better preserved after cold flush with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher and the urinary excretion of trimethylamine-N-oxide and dimethylamine, used as markers of renal medulla injury, were lower in animals transplanted with kidneys cold-flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial and peritubular inflammation and the numbers of infiltrating mononuclear CD45+and CD3+ T cells. These results indicate that the tissue damage due to ischemia/reperfusion injury may be prevented, at least in part, by adding TMZ to preservation solutions.     

Mycophenolate mofetil attenuates renal ischemia/reperfusion injury

Immunosuppressive agents may have an impact on ischemia/reperfusion (I/R) injury. The immunosuppressant mycophenolate mofetil (MMF) presents properties that can attenuate such injury. This study investigated the effects of MMF on renal I/R injury. Male Wistar rats received MMF (20 mg/kg per d) or vehicle by gavage beginning 2 d before ischemia and maintained during the entire study. Ischemic injury was induced by bilateral renal arteries occlusion for 60 min. Control rats received MMF and underwent sham operation. At days 1, 2, and 14, post-ischemia renal function was assessed and kidneys were removed for histologic and immunohistochemical studies. MMF given to nonischemic rats did not alter renal function. There was no functional protection at 24 h post-ischemia with MMF. At 2 d, post-ischemia rats pretreated with MMF presented higher inulin clearance compared with untreated rats (0.42 +/- 0.04 versus 0.15 +/- 0.02 ml/min per 100 g; P < 0.001) and attenuated renal blood flow decrease (5.23 +/- 0.28 versus 3.24 +/- 0.37 ml/min; P < 0.01). The immunostaining for intercellular adhesion molecule-1 (ICAM-1) was less intense in rats pretreated with MMF. These rats also presented an earlier decreased infiltrating macrophages/lymphocytes and cell proliferation at day 1 post-ischemia. The functional and immunohistochemical analyses performed at day 14 post-ischemia returned to values similar to controls in both groups of rats. To determine whether mycophenolic acid (MPA) could induce cytoprotection, the effects of MPA on normoxic and hypoxic/reoxygenated (H/R) isolated tubule suspensions were also investigated. MPA was not deleterious to normoxic tubules and it was not protective against H/R tubules. In conclusion, pretreatment with MMF attenuates I/R injury in rats and does not limit the recovery from ischemia. The protective effect of MMF by reducing inflammation precedes the hemodynamic changes and tubular injury.     

Earlier renal fibrosis aggravates acute kidney injury induced by ischemia reperfusion in mice

Objective To investigate the influence of earlier renal fibrosis on ischemia and reperfusion induced acute kidney injury. Methods Male C57BL/6 mice at eight to twelve weeks old age were divided into 4 groups randomly: (1)Sham (n=3); (2)Unilateral ureter obstruction (UUO, n=6): UUO for 3 days (UUO3d, n=3) and UUO for 5 days (UUO5d, n=3);(3)Ischemia and reperfusion (IR, n=7): bilateral kidney ischemia for 40 minutes followed by 24 hours of reperfusion; (4)UUO for 3 days plus IR (UUO3d+IR, n=6): bilateral kidney ischemia after UUO 2 days for 40 minutes followed by 24 hours of reperfusion, and the real time for UUO was 3 days. Pathologic analysis for acute or chronic injury was performed on paraffin embedded kidney sections with hematoxylin and eosin (HE) or Masson staining. Apoptosis was detected by immunohistochemistry(IHC) and Western blotting with anti-caspase-3 antibody, and proliferation was observed by IHC with anti-ki67 antibody. Results On kidney sections with HE or Masson staining, it showed that the chronic kidney lesions and fibrosis got more severe as time of UUO prolonged from 3 days to 5 days; the area of matrix deposition increased in UUO5d and UUO3d mice significantly compared to Sham mice (P＜0.05) and was smaller in UUO3d mice compared with UUO5d mice obviously (P＜0.05). Acute kidney injury could be observed in UUO3d+IR mice, such as massive inflammatory cells infiltration, tubules dilation, brush border disappearance, tubular epithelial cells vacuolar degeneration, necrosis, casting formation, coexisting with chronic lesions: thinner cortex, broadened interstitial space, and increased blue stained matrix. Acute kidney injury score in UUO3d+IR mice was higher than that in IR mice significantly (P＜0.05), and serum creatinine level increased significantly in UUO3d+IR mice compared to Sham mice (P＜0.05). Caspase-3 expression increased and ki67 positive tubular cells decreased in UUO3d+IR mice than those in IR mice obviously (P＜0.05). Conclusion Earlier renal fibrosis aggravates acute kidney injury induced by ischemia reperfusion in mice through increasing apoptosis and decreasing proliferation of tubular epithelial cells.     

臭氧氧化预处理对大鼠肾脏缺血再灌注损伤致细胞凋亡的影响

目的 观察臭氧氧化预处理对大鼠肾脏缺血再灌注损伤导致的细胞凋亡的影响.方法 分为3组进行实验:(1)假手术组:切除大鼠右肾,缝合腹壁;(2)缺血再灌注组:切除大鼠右肾后,夹闭左肾动、静脉45 min,然后开放;(3)臭氧氧化预处理组:手术步骤与缺血再灌注组相同,在术前15d开始经直肠吹入氧气和臭氧的混合气体5～5.5 ml(臭氧浓度为50 mg/L,1 mg·kg-1 ·d-1),应用至术前1d.全自动生化分析仪检测3组大鼠血清尿素氮和肌酐,比色法测定血清脂质过氧化产物丙二醛(MDA)和超氧化物歧化酶(SOD).免疫组织化学法检测大鼠肾细胞胞浆细胞色素C(CytC)的表达,蛋白质印迹法检测CytC的含量.逆转录聚合酶链反应法检测肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6 (IL-6) mRNA的表达.结果 缺血再灌注和臭氧氧化预处理组血清尿素氮、肌酐和MDA均高于假手术组,而缺血再灌注组的尿素氮、肌酐和MDA又高于臭氧氧化预处理组.缺血再灌注组血清SOD低于假手术组和臭氧氧化预处理组(P＜0.05).臭氧氧化预处理组的肾组织病理学改变较缺血再灌注组轻.假手术组、缺血再灌注组和臭氧氧化预处理组的CytC表达灰度值分别为101.50±18.02、181.00±20.85和156.71±16.82,两两比较,差异均有统计学意义(P＜0.05).臭氧氧化预处理组肾细胞胞浆和线粒体中CytC含量较缺血再灌注组有所下降(P＜0.05).结论 臭氧氧化预处理可以减轻肾脏脂质过氧化反应,减少炎症因子的合成,抑制CytC的释放,减轻肾缺血再灌注损伤.     

Augmentation of ischemia/reperfusion injury to endothelial cells by cyclosporin A

Ischemia/reperfusion (I/R) carries significant injury to endothelial cells in transplanted organs and is an important factor in chronic rejection. Immunosuppressive drugs, notably cyclosporin A (CyA) and FK506, can potentially augment this injury. Here, our goal was to determine the combined effects of I/R and CyA or FK506 on endothelial cells. Transformed mouse endothelial cells (SVEC 4-10) were subjected to ischemia or I/R for 2-24 hours by incubating cells in 100 per cent N2 (ischemia) followed by 5 per cent CO2 and 95 per cent O2 (reperfusion) for 24 hours. In separate experiments, CyA or FK506 was added to cells subjected to ischemia or I/R. Nonviable cells were determined by Trypan blue exclusion assay. All experiments (done in triplicate) were analyzed by Student's t test. Increasing ischemia times resulted in a greater number of nonviable cells (2% nonviable cells at 0 hours and 57% at 24 hours of I/R). Addition of CyA significantly increased the number of nonviable cells when compared with the control (I/R only) group (P = 0.014). Interestingly, FK506 did not increase the percentage of nonviable cells compared with the control group (P = 0.2). Unlike FK506, CyA augments I/R injury to endothelial cells in vitro. These findings could be relevant in chronic rejection and transplantation.     

Distant effects of experimental renal ischemia/reperfusion injury

Acute renal failure results in significant morbidity and mortality, yet renal failure is not the usual cause of death in the clinical situation. We have previously reported systemic increases in the inflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) after renal ischemia in the mouse. In the present study, an animal model of bilateral renal ischemia was used to test the hypothesis that cytokines released with renal ischemia have effects on other organ systems. Increased levels of immunoreactive TNF-alpha and IL-1 and intercellular adhesion molecule-1 mRNA were found in the heart after renal ischemia in the rat. This was accompanied by increases in myeloperoxidase activity, an index of tissue leukocyte infiltration, in the heart as well as the liver and lung. Functional changes in the heart 48 h after renal ischemia included increases in left ventricular end diastolic diameter, left ventricular end systolic diameter, and decreased fractional shortening by echocardiography. Evidence of apoptosis of cardiac cells was also found 48 h after an abbreviated period of renal ischemia insufficient to induce azotemia but not bilateral nephrectomy (which resulted in significant renal failure), suggesting that renal ischemia but not uremia is necessary for the apoptosis observed. It was also found that blocking the action of TNF-alpha limited cardiac apoptosis. Renal ischemia results in distant effects and the alterations observed in the heart may be important in the morbidity and mortality observed clinically.     

瘦素在肝缺血/再灌注致肾损伤中作用的研究

目的：研究瘦素（Leptin）在肝缺血/再灌注（I/R）后肾组织中的表达变化,探讨其与肝I/R介导的肾损伤的关系。方法：建立大鼠70%肝I/R模型,设立假手术和缺血60min后再灌注60、150、240、360min组,观察肾脏的病理学变化,检测各组血清尿酸、总抗氧化能力,肾Leptin蛋白及其mRNA表达的变化。结果：与假手术组比较,缺血60min/再灌注150min及再灌注240min组血清尿酸显著升高,以再灌注240min升高最为显著;再灌注240min和360min组血清总抗氧化能力显著升高,以再灌注240min升高最为显著;再灌注150、240和360min组肾Leptin蛋白表达显著升高,再灌注60、240、360min组肾LeptinmRNA表达显著升高,而再灌注150min组LeptinmRNA显著降低。病理学观察提示肝I/R早期的肾损伤较重而后期显著减轻。结论：Leptin在肝I/R后肾组织内的表达变化与肾损伤密切相关,提示它可能作为一种保护因子对抗肝I/R介导的肾损伤。     

替普瑞酮对大鼠肾脏缺血再灌注损伤的保护作用

目的 探讨替普瑞酮对肾脏缺血再灌注损伤的保护作用和可能机制。 方法 应用替普瑞酮(400 mg/kg)诱导雄性SD大鼠肾脏高表达热休克蛋白72（HSP72）。以钳夹大鼠左肾蒂45 min后，松开血管夹并切除右肾，建立大鼠缺血再灌注肾脏损伤模型。假手术组为打开腹腔，分离肾血管周围组织，但不钳夹血管。模型建立后24 h处死大鼠，留取血清测血肌酐（Scr）和尿素氮（BUN）。肾组织石蜡切片行PAS染色，以损伤肾小管所占百分比评分法评估肾组织肾小管损伤程度。TUNEL法检测缺血再灌注损伤时肾脏细胞凋亡的发生情况。Western印迹检测X连锁凋亡抑制蛋白（XIAP）的水平。 结果 缺血再灌注损伤可导致急性肾衰竭，表现为血Scr、BUN明显升高（P < 0.01）；PAS染色显示外髓部有大片肾小管坏死，甚至出现基底膜裸露；TUNEL染色中肾小管上皮细胞TUNEL阳性细胞数明显增多（P < 0.01）；Western印迹结果显示，肾组织XIAP蛋白水平明显降低（P < 0.01）。替普瑞酮处理后，肾组织HSP72表达水平明显增高（P < 0.01）；缺血再灌注所致的肾脏损伤明显改善，包括肾小管的损伤、细胞凋亡以及肾功能。此外，替普瑞酮可稳定肾组织XIAP的蛋白水平（P < 0.05）。 结论 替普瑞酮可诱导肾脏高表达HSP72。替普瑞酮可能通过减少肾脏XIAP蛋白的降解，抑制细胞凋亡，减轻缺血再灌注的肾脏损伤。     

Nebivolol reduces experimentally induced warm renal ischemia reperfusion injury in rats

Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. The objective of the present study was to examine the role of nebivolol in modulating peroxynitrite species-induced inflammation and apoptosis after renal warm ischemia/reperfusion injury in rats. The present study was designed to investigate the effects of nebivolol on the renal warm ischemia/reperfusion injury in rats treated with the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester. After right nephrectomy, nebivolol was administered for 15 days. On the 16(th) day, ischemia was induced in contra lateral kidney for 45 min, followed by reperfusion for 24 hr. Renal function, inflammation, and apoptosis were estimated at the end of 24 hr reperfusion. Nebivolol improved the renal dysfunction and reduced inflammation and apoptosis after renal ischemia/reperfusion injury. In conclusion, nebivolol shows potent anti-apoptotic and anti-inflammatory properties due to its NO-releasing property. These findings may have major implications in the treatment of human ischemic acute renal failure.     

Effect of apigenin on apoptosis induced by renal ischemia/reperfusion injury in vivo and in vitro

Objectives: This study aims to investigate the effects and molecular mechanisms of apigenin (ApI) on renal ischemia/reperfusion (I/R) injury in vivo and in vitro.

Methods: In vivo, the left renal artery was clamped for 45?min and the right kidney was removed to study renal I/R injury on Sprague-Dawley (SD) rats. ApI was injected at 60?min before renal ischemia. In vitro, renal tubular epithelial cells (HK-2) were pretreated with or without ApI (20 uM) for 60?min and then treated with hypoxia/reoxygenation (H/R). Renal function, histology, cells apoptosis, and cell viability were tested. Furthermore, the potential molecular mechanisms were assessed.

Results: ApI pretreatment could significantly alleviated the renal function and the pathological damage as well as cells apoptosis after I/R injury. Meanwhile, ApI treatment protects H/R induced HK-2 cell apoptosis in vitro. The results of Western blot showed that ApI significantly increased the expressions of B-cell lymphoma 2 (Bcl-2) and phosphor-AKt (p-AKt), Phosphoinositide 3-kinase (PI3K), while down-regulated the expressions of Caspase3 and Bax induced by H/R injury.

Conclusions: ApI pretreatment can protect renal function against I/R injury and prevent renal tubular cells from apoptosis in vivo and in vitro which might through PI3K/Akt mediated mitochondria-dependent apoptosis signaling pathway.     

Hydrogen sulfide reduce renal ischemia/reperfusion injury by NOD-like receptor pathway

Objective To investigate whether the nod-like receptor (NLR) pathway is involved in protection of hydrogen sulfide (H2S) preconditioning during renal ischemia reperfusion. Methods Male Wistar rats were randomly divided into 3 groups: sham operation (Sham) group, renal ischemia/reperfusion (I/R) group subjected to occlusion of left renal pedicle for 45 min then reperfusion for 24 hours, and sodium hydrosulfide (NaHS) preconditioning group with continuous infusion of NaHS (300 nmol/min) by left renal artery for 15 min before I/R treatment. Renal injuries were evaluated by HE staining. The protein levels of NOD1, NOD2, nuclear NF-κB P65 and caspase-1 were analyzed by Western blot assay. The protein level of MCP-1 and IL-1β expressions was determined by immunohistochemical staining assay. Cell apoptosis were evaluated by Tunel staining assay. Results In I/R group, the renal NOD1 and NOD2 protein expressions were upregulated. Moreover, the nuclear NF-κB P65 expression was also elevated with an increase in its target genes-MCP-1 and IL-1β (All P＜0.01). HE staining revealed the existence of acute tubular necrosis in I/R kidney. TUNEL staining revealed more apoptotic cells in risk zone with the activation of caspase-1 of I/R-treated kidney(P＜0.01). NaHS preconditioning reversed I/R-induced increase in the expression of NOD1 and NOD2(P＜0.05). NaHS preconditioning also reduced I/R-induced activation of NF-κB P65 (P＜0.05) and upregulation of MCP-1 and IL-1β (P＜0.01). Moreover, NaHS preconditioning attenuated inflammation, repressed caspase-1 activation and reduced apoptotic cells after I/R. Conclusion Hydrogen sulfide preconditioning can alleviate renal ischemia/reperfusion injury by Nod-like receptor dependent on inflammatory pathway.     

大鼠肝缺血及再灌注所致小肠过氧化损伤及丹参的保护作用

目的 观察大鼠肝缺血再灌注小肠过氧化损伤及丹参预处理的保护作用.方法 首先将SD大鼠随机分为正常对照组(CO组)、假手术组(SO组)、缺血再灌注组(IR组)、丹参预处理组(SM组),分别在肝缺血30、45、60 min时取上段空肠进行大体病理学检测;然后在肝缺血45 min条件下,动物亦随机分为4组(CO组、SO组、IR组、SM组),按再灌注后不同时间(0、3、12、24、72 h)分为5个亚组,每组5只.SM组在阻断第一肝门30 min前经尾静脉推注丹参注射液6 g/kg加生理盐水40 ml/kg,其余各组按40 ml/kg给予生理盐水尾静脉注入,SO组开腹后仅解剖肝门,不钳夹肝蒂.分别在再灌注0、3、12、24、72 h取上段空肠行病理学检查、丙二醛(MDA)含量测定、髓过氧化物酶(MPO)活性测定.结果 空肠黏膜损伤评分随肝缺血时限延长而加重;在肝缺血45 min再灌注不同时限点SM组空肠黏膜损伤较IR组明显减轻,且肠组织MDA含量、MPO活性均低于IR组(P<0.05).结论 肝缺血再灌注所致小肠明显淤血性损伤,MDA含量、MPO活性升高,丹参预处理对肝缺血再灌注所致小肠损伤具有保护作用.     

Mitochondrial defects by intracellular calcium overload versus endothelial cold ischemia/reperfusion injury

Abstract Questions as to the critical stress factor and primary targets of cold ischemia/reperfusion (CIR) injury were addressed by comparing mitochondrial defects caused by (1) CIR injury and (2) intracellular Ca²⁺ overload. CIR was simulated in transformed human umbilical vein endothelial cell cultures (tEC) by 8 h cold anoxia in University of Wisconsin solution and reoxygenation at 37°C. Intracellular Ca²⁺ concentrations were changed by permeabilization of suspended cells with digitonin in culture medium (RPMI, 0.4 mM Ca²⁺). Binding of free Ca²⁺ by ethylene glycol‐bis(β‐aminoethylether)‐N,N,N',N'‐tetraacetic acid in RPMI or mitochondrial incubation medium served as controls. Extracellular Ca²⁺ protected the cell membrane against permeabilization. Mitochondrial functions were determined before and after permeabilization of the cell membrane. After CIR, mitochondrial respiratory capacity declined, but oxygen consumption remained coupled to adenosine triphosphate (ATP) production. In contrast, Ca²⁺ overload caused uncoupling of mitochondrial respiration. High intracellular Ca²⁺ overload, therefore, does not reproduce cold ischemia/reperfusion injury in endothelial cells.     

Effects of amrinone on bilateral renal ischemia/reperfusion injury

Renal ischemia/reperfusion injury could arise as a consequence of clinical conditions such as renal transplantation, shock, cardiac arrest, hemorrhage and renal artery surgery. In this experimental study, we aimed to determine the preventive effects of amrinone on bilateral renal ischemia/reperfusion injury in rats. A total of 60 Wistar-albino rats were divided into six groups ( n=10). Midline laparotomies were made under ketamine anesthesia. In the sham, amrinone1 and amrinone2 without ischemia (AWI1 and AWI2) groups saline, 5 and 10 mg/kg of amrinone was infused, respectively. In the ischemia, ischemia plus amrinone1 (IPA1) and ischemia plus amrinone2 (IPA2) groups, saline and 5 and 10 mg/kg of amrinone was infused, respectively, at the beginning of reperfusion, subsequent to 45 min of bilateral renal artery occlusion. Following 6 h of reperfusion, blood was drawn to study serum BUN and creatinine and a bilateral nephrectomy was done to determine tissue malonyldialdehyde ( MDA) and myeloperoxidase (MPO) levels. The results were analysed by Mann-Whitney U-test. The parameters studied were statistically higher in the ischemia group compared with the other groups ( P<0.05 for each comparison), indicating renal I/R injury. These parameters were lower in the amrinone without ischemia groups (AWI1 and AWI2) than in the sham group, however there were no significant differences between the groups ( P>0.05, for each comparison). The treatment groups IPA1 and IPA2 had statistically similar results compared with the sham group, showing the preventive effect of amrinone on renal I/R injury at the given doses. We conclude that amrinone prevented experimental renal ischemia/reperfusion injury in rats, independently of the administered doses. This preventive effect of the agent could depend on its effect of regulating the microcirculation, in decreasing intracellular calcium and in preventing neutrophil activation. We propose that this preventive effect of amrinone - which has gained clinical application especially in cases of cardiac insufficiency - could also be exploited in clinical conditions related with renal ischemia/reperfusion.