Format

Send to

Choose Destination
Korean J Intern Med. 2009 Sep;24(3):238-46. doi: 10.3904/kjim.2009.24.3.238. Epub 2009 Aug 26.

Pretreatment with darbepoetin attenuates renal injury in a rat model of cisplatin-induced nephrotoxicity.

Author information

1
Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.

Abstract

BACKGROUND/AIMS:

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.

KEYWORDS:

Apoptosis; Cisplatin; Darbepoetin alfa; Inflammation

PMID:
19721861
PMCID:
PMC2732784
DOI:
10.3904/kjim.2009.24.3.238
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Publishing M2Community Icon for PubMed Central
Loading ...
Support Center