title: Chronic lithium treatment protects the rat kidney against ischemia/reperfusion injury: the role of nitric oxide and cyclooxygenase pathways.
abstract: Ischemia/reperfusion injury is a major problem in renal transplantation. Several evidences represent lithium preconditioning effect against ischemia/reperfusion injury in various tissues. In this study our aim was to investigate the protective effect of chronic lithium administration on renal ischemia/reperfusion injury in rats. Ischemia/reperfusion injury was induced by clamping left renal pedicle for 60 min, 2 weeks after right nephrectomy. Lithium-treated animals received lithium-chloride in drinking water for 30days. In order to investigate the role of nitric oxide (NO) and cyclooxygenase (COX) pathways in renoprotective effect of lithium, N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME, NO synthase inhibitor) and indomethacin (COX inhibitor) were used, respectively. Serum creatinine, blood urea nitrogen and renal histology were assessed 24h after inducing ischemia/reperfusion injury. Dimercaptosuccinic acid scan was also performed 48 h following operation. Chronic lithium treatment in ischemia/reperfusion injury groups significantly decreased creatinine (1.09±0.16 mg/dl), blood urea nitrogen (59.0±13.38 mg/dl), histological damage (7.83%±4.02%) and improved cortical function compared with non-lithium treated animals (4.45±0.44, 176.66±12.24 mg/dl and 83.5%±3.5%, respectively) (P<0.001). Either L-NAME or indomethacin administration partially reversed the protective effect of lithium, while simultaneous blockade of NO and COX pathways completely abolished lithium renoprotective effect. Our results indicate that lithium ameliorates renal ischemia/reperfusion injury through NO and/or COX pathways. We propose that lithium pre-treatment as a simple and practical intervention to boost the renal viability and function after ischemia/reperfusion injury may be promising in the setting of transplantation.
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: Hamed
authors.initials: H
authors.lastname: Emami
authors.forename: Azadeh
authors.initials: A
authors.lastname: Elmi
authors.forename: Behtash Ghazi
authors.initials: BG
authors.lastname: Nezami
authors.forename: Solmaz
authors.initials: S
authors.lastname: Assa
authors.forename: Armin Farajzadeh
authors.initials: AF
authors.lastname: Deroee
authors.forename: Ali
authors.initials: A
authors.lastname: Daneshmand
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 / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018021:Lithium Chloride / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000494:pharmacology; D020011:Protective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D018692:Antimanic Agents; D016861:Cyclooxygenase Inhibitors; D020011:Protective Agents; D009569:Nitric Oxide; D003404:Creatinine; D011451:Prostaglandin-Endoperoxide Synthases; D018021:Lithium Chloride