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

  • S.S. T
  • A. E
  • H. E
 et al. 
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Abstract

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. © 2012 Elsevier B.V. All rights reserved.

Author-supplied keywords

  • acute drug administration
  • animal experiment
  • animal model
  • animal tissue
  • article
  • controlled study
  • creatinine
  • creatinine blood level
  • dose response
  • drug blood level
  • drug effect
  • drug mechanism
  • histopathology
  • indometacin
  • ischemic preconditioning
  • kidney ischemia
  • lithium chloride
  • male
  • n(g) nitroarginine methyl ester
  • nitric oxide
  • nitrogen
  • nonhuman
  • priority journal
  • prostaglandin synthase
  • protein function
  • rat
  • renal protection
  • reperfusion injury
  • signal transduction
  • single drug dose
  • urea
  • urea nitrogen blood level

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Authors

  • Talab S.S.

  • Elmi A.

  • Emami H.

  • Nezami B.G.

  • Assa S.

  • Ghasemi M.

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