Melatonin with 1,25-dihydroxyvitamin D3 protects against apoptotic ischemia-reperfusion injury in the rat kidney.
This study was designed to evaluate the preventive role of melatonin (Mel) and 1,25-dihydroxyvitamin D3 (VD3) in biochemical and apoptotic events leading to tissue injury and renal dysfunction after ischemia-reperfusion (I/R). Thirty male Wistar rats were divided into five groups: sham-operated, I/R, Mel + I/R, VD3 + I/R, and Mel + VD3 + I/R. The rats were intraperitoneally administered with Mel (10 mg/kg), VD3 (0.5 μg/kg), or Mel (10 mg/kg) plus VD3 (0.5 μg/kg) each day at 1 week prior to ischemia. Right nephrectomy was initially performed and left renal I/R injury was induced by 45 min of bilateral renal ischemia followed by 45 min of reperfusion. After reperfusion, kidneys and blood were obtained for histopathologic and biochemical evaluation. Mel and VD3 had an ameliorative effect on biochemical parameters such as serum creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, and apoptosis (caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining) in the kidneys against renal I/R injury in rats. Additionally, VD3 combined with Mel significantly reduced apoptotic and histological alterations when compared with Mel or VD3 alone. This preventive effect on renal tubular apoptosis was remarkable when Mel was combined with VD3.
Department of Urology, Faculty of Medicine, Maltepe University, Maltepe, Istanbul, Turkey.
Orhun
O
Sinanoglu
Gulbuz
G
Sezgin
Guler
G
Ozturk
Matem
M
Tuncdemir
Sevin
S
Guney
Fehime Benli
FB
Aksungar
Nese
N
Yener
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002117:Calcitriol / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000032:analysis; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000517:prevention & control*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
D000975:Antioxidants; D053148:Caspase 3; D002117:Calcitriol; D008550:Melatonin