Karaman Abdurrahman, Turkmen Emine, Gursul Cebrail, Tas Erkan, Fadillioglu Ersin
Inonu University, Faculty of Medicine, Department of Pediatric Surgery, Malatya, Turkey.
Int J Urol. 2006 Nov;13(11):1434-41. doi: 10.1111/j.1442-2042.2006.01592.x.
There is increasing evidence to suggest that toxic oxygen radicals play an essential role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of leflunomide, an isoxazole derivative and a unique immunomodulatory agent, in I/R-induced renal injury in rats.
Forty female Sprague-Dawley rats were divided equally into four groups: (I) control (only leflunomide 10 mg/kg, intragastrically treated); (II) sham operated (only unilateral nephrectomy); (III) I/R; and (IV) leflunomide (10 mg/kg for two doses prior to experiment) plus I/R groups. In groups III and IV, after unilateral nephrectomy, the rats were subjected to 60 min of left renal pedicle occlusion, followed by 6 h of reperfusion. At the end of the reperfusion period, rats were killed and kidneys and blood were removed. Catalase, myeloperoxidase and xanthine oxidase activities, and malondialdehyde, nitric oxide and protein carbonyl levels were determined in renal tissue. Serum creatinine, blood urea nitrogen and aspartate aminotransferase were measured for the evaluation of renal function. In histopathological examination, renal damage was scored 0-3.
Group III animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with leflunomide markedly attenuated renal dysfunction, morphological alterations, reduced elevated oxidative stress products levels and restored the depleted renal antioxidant enzyme.
The findings imply that oxygen radicals play a causal role in I/R-induced renal injury, and leflunomide exerts renoprotective effects probably by the radical scavenging and antioxidant activities with immunomodulatory effect.
越来越多的证据表明，毒性氧自由基在肾脏缺血/再灌注（I/R）损伤的发病机制中起重要作用。本研究旨在探讨异恶唑衍生物及独特免疫调节剂来氟米特对大鼠I/R诱导的肾损伤的影响。
40只雌性Sprague-Dawley大鼠平均分为四组：（I）对照组（仅经口给予来氟米特10 mg/kg）；（II）假手术组（仅行单侧肾切除术）；（III）I/R组；（IV）来氟米特组（实验前给予两剂10 mg/kg）加I/R组。在III组和IV组中，单侧肾切除术后，大鼠左肾蒂闭塞60分钟，然后再灌注6小时。再灌注期结束时，处死大鼠并取出肾脏和血液。测定肾组织中的过氧化氢酶、髓过氧化物酶和黄嘌呤氧化酶活性，以及丙二醛、一氧化氮和蛋白质羰基水平。检测血清肌酐、血尿素氮和天冬氨酸转氨酶以评估肾功能。在组织病理学检查中，肾损伤评分为0-3分。
III组动物表现出严重的肾功能恶化、肾脏形态改变和明显的肾脏氧化应激。用 来氟米特预处理动物可显著减轻肾功能障碍、形态学改变，降低氧化应激产物水平升高，并恢复耗尽的肾脏抗氧化酶。
这些发现表明氧自由基在I/R诱导的肾损伤中起因果作用，来氟米特可能通过清除自由基和抗氧化活性以及免疫调节作用发挥肾保护作用。
