Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantation

• Published in: Journal of pineal research 2009-05, Vol.46 (4), p.365-372
• Main Authors: Li, Zhanqing, Nickkholgh, Arash, Yi, Xue, Bruns, Helge, Gross, Marie-Luise, Hoffmann, Katrin, Mohr, Elvira, Zorn, Markus, Büchler, Markus W., Schemmer, Peter
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cardiology. Vascular system; caspase; Caspase 3 - metabolism; Fundamental and applied biological sciences. Psychology; Histocytochemistry; iNOS; ischemia/reperfusion injury; Kaplan-Meier Estimate; Kidney - metabolism; kidney transplantation; Kidney Transplantation - methods; Lipid Peroxidation - drug effects; Male; Medical sciences; melatonin; Melatonin - pharmacology; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-kB; Nitric Oxide Synthase Type II - metabolism; Oxidative Stress; radical scavenger; Random Allocation; Rats; Rats, Inbred Lew; Renovascular diseases; Reperfusion Injury - blood; Reperfusion Injury - prevention & control; Superoxide Dismutase - metabolism; Transplantation Conditioning - methods; tubular damage; Vertebrates: endocrinology
• ISSN: 0742-3098; 1600-079X
• DOI: 10.1111/j.1600-079X.2009.00672.x

:  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