Protective effects of acute lithium preconditioning against renal ischemia/reperfusion injury in rat: Role of nitric oxide and cyclooxygenase systems

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• 作者：Saman Shafaat Talab^a ; Azadeh Elmi^a ; Hamed Emami^a ; Behtash Ghazi Nezami^a ; Solmaz Assa^a ; Mehdi Ghasemi^a ; Seyed Mohammad Tavangar^b ; Ahmad Reza Dehpour^a ; ^{dehpour@yahoo.com}
• 关键词：Cyclooxygenase ; Ischemia/reperfusion ; Kidney ; Lithium ; Nitric oxide ; (Rat)
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：15 April, 2012
• 卷：681
• 期：1-3
• 页码：94-99
• 文件大小：858 K

摘要

Delayed graft function secondary to ischemia/reperfusion injury has been shown to be associated with increased rate of allograft failure following kidney transplantation. Previously, we have shown that chronic lithium pretreatment protects kidney against ischemia/reperfusion injury. In the present study we aimed to examine the effects of acute lithium administration on the renal ischemia/reperfusion injury in rat. Ischemia/reperfusion injury was induced by clamping left renal pedicle for 60 min, two weeks after right nephrectomy. The mechanism of lithium-mediated renoprotection was explored by combined use of lithium and nitro-l-arginine methyl ester (L-NAME) (non-selective nitric oxide synthase inhibitor) and/or indomethacin (non-selective cyclooxygenase pathway inhibitor). Lithium-treated animals were given 40 mg/kg lithium chloride intraperitoneally, 30 min before ischemia. To investigate the role of nitric oxide and cyclooxygenase pathways in renoprotective effect of lithium, L-NAME and/or indomethacin were administered before lithium injection. Serum creatinine, blood urea nitrogen, and renal histology were assessed after 24 h of reperfusion. Lithium preconditioning significantly reduced creatinine and blood urea nitrogen (P < 0.001) and improved renal histology. Administration of L-NAME completely reversed renoprotective effect of lithium. In contrast indomethacin significantly potentiated the lithium renoprotection. Moreover, co-administration of L-NAME and indomethacin completely abolished the protective effects of lithium. The results show that a single dose of lithium significantly improves renal function following ischemia/reperfusion injury. In conclusion, the ability of lithium to enhance renal tissue tolerance against ischemia/reperfusion injury suggests a potential clinical application in the setting of kidney transplantation. However, more detailed investigations are required before any definite conclusion.