title: Pretreatment with darbepoetin attenuates renal injury in a rat model of cisplatin-induced nephrotoxicity.
abstract: OBJECTIVE
  Darbepoetin alpha (DPO) exhibits comparable renoprotective effects to erythropoietin (EPO) in several animal models of acute renal injury. We examined whether DPO also attenuated renal injury in a rat model of cisplatin nephrotoxicity.
  
  
  METHODS
  Male Sprague-Dawley rats were divided into four groups: untreated, DPO-treated, cisplatin-injected, and DPO-treated cisplatin-injected. DPO pretreatment was conducted 24 hours after and just before cisplatin administration. Ninety-six hours after cisplatin administration, animals in all experimental groups were sacrificed. We examined serology; real-time reverse transcription polymerase chain reaction (RT-PCR) for TNF-alpha, Bcl-2, and MCP-1 gene expression; and Western blots for caspase-3. We also conducted terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and light microscopy.
  
  
  RESULTS
  Pretreatment with DPO significantly reduced the levels of blood urea nitrogen and serum creatinine, the magnitude of renal tubular epithelial damage, and renal gene expression of TNF-alpha, Fas, and MCP-1 in kidneys injured by cisplatin. Pretreatment with DPO significantly increased Bcl-2 mRNA levels in kidneys injured by cisplatin, and significantly reduced activated caspase-3 and TUNEL-positive cells.
  
  
  CONCLUSIONS
  DPO exhibits a renoprotective effect in experimental cisplatin-induced renal injury, the mechanism of which may involve DPO antiinflammatory and antiapoptotic effects.
authors.affiliation: Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Dae Eun
authors.initials: DE
authors.lastname: Choi
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Jeong
authors.forename: Beom Jin
authors.initials: BJ
authors.lastname: Lim
authors.forename: Kang Wook
authors.initials: KW
authors.lastname: Lee
authors.forename: Young-Tai
authors.initials: YT
authors.lastname: Shin
authors.forename: Ki-Ryang
authors.initials: KR
authors.lastname: Na
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006400:Hematocrit; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D002945:Cisplatin