title: Protective effects of acute lithium preconditioning against renal ischemia/reperfusion injury in rat: role of nitric oxide and cyclooxygenase systems.
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 24h 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saman Shafaat
authors.initials: SS
authors.lastname: Talab
authors.forename: Azadeh
authors.initials: A
authors.lastname: Elmi
authors.forename: Hamed
authors.initials: H
authors.lastname: Emami
authors.forename: Behtash Ghazi
authors.initials: BG
authors.lastname: Nezami
authors.forename: Solmaz
authors.initials: S
authors.lastname: Assa
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghasemi
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Tavangar
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D007213:Indomethacin / Q000494:pharmacology; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
chemical_list: D018692:Antimanic Agents; D020011:Protective Agents; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D018021:Lithium Chloride; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin