TY - JOUR
T1 - Efficacy of darbepoetin in doxorubicin-induced cardiorenal injury in rats
AU - Noiri, Eisei
AU - Nagano, Nobuo
AU - Negishi, Kosuke
AU - Doi, Kent
AU - Miyata, Sonoe
AU - Abe, Megumi
AU - Tanaka, Tamami
AU - Okamoto, Koji
AU - Hanafusa, Norio
AU - Kondo, Yasushi
AU - Ishizaka, Nobukazu
AU - Fujita, Toshiro
PY - 2006/8
Y1 - 2006/8
N2 - This study was intended to elucidate the efficacy of an erythropoietin analog in cardiorenal dysfunction syndrome using a rodent model. Cardiorenal dysfunction was induced using doxorubicin hydrochloride (DXR). Lower doses (3 μg/kg) and higher doses (30 μg/kg) of darbepoetin alfa (DA) were used for intervention. Blood examinations for creatinine, blood urea nitrogen, iron, and hemoglobin were performed until 11 weeks after starting DA administration. Urine collection was performed 10 weeks after starting DA, and protein, iron, and N-acetyl-β-D-glucosaminidase levels and antioxidation capacity of DA were determined. The dry left ventricular heart weight was measured, when the animals were sacrificed 11 weeks after starting DA administration. Histological analyses were performed for interstitial fibrotic changes and iron deposition in the kidney. Administration of DA markedly improved anemia to the normal control level and significantly alleviated DXR-induced increases of creatinine, blood urea nitrogen, renal interstitial fibrosis, renal iron deposition, and dry left ventricular weight, but serum and urinary iron and urinary protein and N-acetyl-β-D-glucosaminidase levels were unchanged. The urinary total radical-trapping antioxidant capacity was improved to the normal control level in DA-treated animals. DA reduced the DXR-induced cardiorenal injury. This improvement was achieved, when anemia was corrected to the normal control level.
AB - This study was intended to elucidate the efficacy of an erythropoietin analog in cardiorenal dysfunction syndrome using a rodent model. Cardiorenal dysfunction was induced using doxorubicin hydrochloride (DXR). Lower doses (3 μg/kg) and higher doses (30 μg/kg) of darbepoetin alfa (DA) were used for intervention. Blood examinations for creatinine, blood urea nitrogen, iron, and hemoglobin were performed until 11 weeks after starting DA administration. Urine collection was performed 10 weeks after starting DA, and protein, iron, and N-acetyl-β-D-glucosaminidase levels and antioxidation capacity of DA were determined. The dry left ventricular heart weight was measured, when the animals were sacrificed 11 weeks after starting DA administration. Histological analyses were performed for interstitial fibrotic changes and iron deposition in the kidney. Administration of DA markedly improved anemia to the normal control level and significantly alleviated DXR-induced increases of creatinine, blood urea nitrogen, renal interstitial fibrosis, renal iron deposition, and dry left ventricular weight, but serum and urinary iron and urinary protein and N-acetyl-β-D-glucosaminidase levels were unchanged. The urinary total radical-trapping antioxidant capacity was improved to the normal control level in DA-treated animals. DA reduced the DXR-induced cardiorenal injury. This improvement was achieved, when anemia was corrected to the normal control level.
KW - Darbepoetin
KW - Doxorubicin-induced cardiorenal injury
KW - Rat model, cardiorenal injury
UR - http://www.scopus.com/inward/record.url?scp=33747279072&partnerID=8YFLogxK
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U2 - 10.1159/000093258
DO - 10.1159/000093258
M3 - Article
C2 - 16707910
AN - SCOPUS:33747279072
VL - 104
SP - e6-e14
JO - Nephron - Experimental Nephrology
JF - Nephron - Experimental Nephrology
SN - 1660-8151
IS - 1
ER -