title: The renoprotective effect of cGMP phosphodiesterase inhibitor and nitroprusside in a rat model of cyclosporin A-induced nephrotoxicity.
abstract: BACKGROUND
  The cyclosporin A (CsA) nephrotoxicity limits its usefulness as an immunosuppression. We studied the administration of both nitroprusside and phosphodiesterase-5 inhibitor (udenafil) in order to determine whether these agents could ameliorate the renal injury in CsA nephrotoxicity.
  
  
  METHODS
  30 8-week-old SD rats were divided into 5 groups: the control (1), SQ with 15 mg/kg CsA (Group 2), CsA along with 5 mg/kg IP nitroprusside (Group 3), CsA with 10 mg/kg PO udenafil (Group 4), and CsA with udenafil and nitroprusside (Group 5).
  
  
  RESULTS
  Group showed an increase in creatinine compared o the control group. Group 5 showed a decrease in creatinine compared to Group 2. In TUNEL, Group 2 increased apoptosis in proximal tubules compared to control. Group 5 showed a decrease in apoptosis compared to Groups 2, 3, and 4. In IHC, the eNOS in Group 2 was stronger than in the controls. Groups 3, 4, and 5 showed decreased staining intensity compared to Group 2. In IHC, the VEGF in Groups 2, 3, and 4 increased compared to the controls. The eNOS protein expression was increased in both Groups 3 and 5 compared to the controls. The VEGF protein expression was increased in Groups 3 and 5 compared to Group 2. The eNOS mRNA was decreased in Group 2 compared to the control group and tended to increase in Groups 3, 4, and 5 compared to Group 2. The VEGF mRNA was increased in Group 2 and tended to increase more in Groups 3 and 5.
  
  
  CONCLUSIONS
  The udenafil and nitroprusside ameliorated renal injury in rat model of CsA nephrotoxicity. The mechanism appears to be associated with decreasing tubular apoptosis by decreasing eNOS and increasing VEGF.
authors: Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Gangwon, South Korea.
authors: Jae Won
authors: JW
authors: Yang
authors: Jae Seok
authors: JS
authors: Kim
authors: Min Keun
authors: MK
authors: Kim
authors: Jun Young
authors: JY
authors: Lee
authors: Byoung-Geun
authors: BG
authors: Han
authors: Seung Ok
authors: SO
authors: Choi
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects; D004195:Disease Models, Animal; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology; D008297:Male; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009599:Nitroprusside / Q000627:therapeutic use*; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D003404:Creatinine; D016572:Cyclosporine; D020030:Nitric Oxide Donors; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside; D058986:Phosphodiesterase 5 Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; C419664:udenafil; D000096926:Benzenesulfonamides