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.