Pretreatment with Darbepoetin Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity.
10.3904/kjim.2009.24.3.238
- Author:
Dae Eun CHOI
1
;
Jin Young JEONG
;
Beom Jin LIM
;
Kang Wook LEE
;
Young Tai SHIN
;
Ki Ryang NA
Author Information
1. Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea. drngr@cnuh.co.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Darbepoetin alfa;
Cisplatin;
Apoptosis;
Inflammation
- MeSH:
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
- From:The Korean Journal of Internal Medicine
2009;24(3):238-246
- CountryRepublic of Korea
- Language:English
-
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.
