Korean J Intern Med.  2009 Sep;24(3):238-246. 10.3904/kjim.2009.24.3.238.

Pretreatment with Darbepoetin Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity

• Choi DE
• Jeong JY
• Lim BJ
• Lee KW
• Shin YT
• Na KR

• KMID: 1717948
• DOI: http://doi.org/10.3904/kjim.2009.24.3.238

Abstract

BACKGROUND/AIMS
Darbepoetin alfa (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 Spague-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.

Keyword

Darbepoetin alfa; Cisplatin; Apoptosis; Inflammation

MeSH Terms

Animals
Anti-Inflammatory Agents/pharmacology
Antineoplastic Agents/*toxicity
Apoptosis/drug effects
Cisplatin/*toxicity
Erythropoietin/*analogs & derivatives/pharmacology
Hematocrit
Kidney/*drug effects/pathology
Male
Rats
Rats, Sprague-Dawley