Efficacy of darbepoetin in doxorubicin-induced cardiorenal injury in rats.
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 microg/kg) and higher doses (30 microg/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-beta-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-beta-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.
Noiri
Eisei
E
Department of Nephrology and Endocrinology, Nephrology 107 Laboratory, Center for Dialysis, Apheresis, and Applied Medicine, University Hospital, Tokyo, Japan. noiri-tky@umin.ac.jp
Nagano
Nobuo
N
Negishi
Kosuke
K
Doi
Kent
K
Miyata
Sonoe
S
Abe
Megumi
M
Tanaka
Tamami
T
Okamoto
Koji
K
Hanafusa
Norio
N
Kondo
Yasushi
Y
Ishizaka
Nobukazu
N
Fujita
Toshiro
T
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D000975:Antioxidants / Q000032:analysis; D006332:Cardiomegaly / Q000473:pathology; D000068256:Darbepoetin alfa; D004317:Doxorubicin; D004906:Erythrocyte Count; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006352:Heart Ventricles / Q000473:pathology; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007501:Iron / Q000652:urine; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014168:Transferrin / Q000652:urine
D000975:Antioxidants; D006454:Hemoglobins; D014168:Transferrin; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D004317:Doxorubicin; D007501:Iron; D000118:Acetylglucosaminidase