title: Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantation.
abstract: Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine-Tryptophan-Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival (P < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39-71% (P < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity.
authors: Department of General Surgery, Ruprecht-Karls University, Heidelberg, Germany.
authors: Zhanqing
authors: Z
authors: Li
authors: Arash
authors: A
authors: Nickkholgh
authors: Xue
authors: X
authors: Yi
authors: Helge
authors: H
authors: Bruns
authors: Marie-Luise
authors: ML
authors: Gross
authors: Katrin
authors: K
authors: Hoffmann
authors: Elvira
authors: E
authors: Mohr
authors: Markus
authors: M
authors: Zorn
authors: Markus W
authors: MW
authors: Büchler
authors: Peter
authors: P
authors: Schemmer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D006651:Histocytochemistry; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation / Q000379:methods*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; D053148:Caspase 3; D008550:Melatonin