Pretreatment with darbepoetin attenuates renal injury in a rat model of cisplatin-induced nephrotoxicity.
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.
Choi
Dae Eun
DE
Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.
Jeong
Jin Young
JY
Lim
Beom Jin
BJ
Lee
Kang Wook
KW
Shin
Young-Tai
YT
Na
Ki-Ryang
KR
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
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D002945:Cisplatin