title: Dose-dependent protective effect of ivabradine against ischemia-reperfusion-induced renal injury in rats.
abstract: OBJECTIVE
  This study was designed to investigate the dose-dependent protective effect of ivabradine, a specific inhibitor of the cardiac sinoatrial node, on renal ischemia-reperfusion (I/R) injury in rats.
  
  
  METHODS
  Rats were divided into six groups: group 1, control; group 2, I/R (60 min ischemia followed by 24 h reperfusion); groups 3 and 4, 0.6-6 mg/kg ivabradine; and groups 5 and 6, sham+0.6-6 mg/kg ivabradine. At the end of the study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase contents were assayed in the kidney tissues; serum blood levels of urea nitrogen (BUN), creatinine (Cr) and albumin also were determined.
  
  
  RESULTS
  Tissue MDA levels were found to be significantly higher in the I/R group, whereas SOD and CAT levels were lower when compared to the control group. Ivabradine (0.6 mg/kg) treatment reduced the MDA levels and elevated the SOD and CAT enzyme activity. Treatment with a dose of 6 mg/kg ivabradine further increased MDA levels and did not ameliorate SOD or CAT activities. Serum levels of BUN and Cr were significantly higher in the I/R group. I/R+0.6 mg ivabradine reduced the elevated BUN and Cr levels.
  
  
  CONCLUSIONS
  This study indicates that ivabradine exerts a dose-dependent response beyond heart rate reduction against renal I/R injury.
authors: Inonu University, Medical Faculty, Department of Urology, Malatya, Turkey. ali.beytur @ inonu.edu.tr
authors: Ali
authors: A
authors: Beytur
authors: Murat
authors: M
authors: Binbay
authors: M Ediz
authors: ME
authors: Sarihan
authors: Hakan
authors: H
authors: Parlakpinar
authors: Alaadin
authors: A
authors: Polat
authors: M Orhun
authors: MO
authors: Gunaydin
authors: Ahmet
authors: A
authors: Acet
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D000077550:Ivabradine; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001552:Benzazepines; D054815:Cyclic Nucleotide-Gated Cation Channels; D000077550:Ivabradine; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase