Efficacy of darbepoetin in doxorubicin-induced cardiorenal injury in rats

Eisei Noiri, Nobuo Nagano, Kosuke Negishi, Kent Doi, Sonoe Miyata, Megumi Abe, Tamami Tanaka, Koji Okamoto, Norio Hanafusa, Yasushi Kondo, Nobukazu Ishizaka, Toshiro Fujita

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)e6-e14
JournalNephron - Experimental Nephrology
Volume104
Issue number1
DOIs
Publication statusPublished - 2006 Aug 1
Externally publishedYes

Keywords

  • Darbepoetin
  • Doxorubicin-induced cardiorenal injury
  • Rat model, cardiorenal injury

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Nephrology

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  • Cite this

    Noiri, E., Nagano, N., Negishi, K., Doi, K., Miyata, S., Abe, M., Tanaka, T., Okamoto, K., Hanafusa, N., Kondo, Y., Ishizaka, N., & Fujita, T. (2006). Efficacy of darbepoetin in doxorubicin-induced cardiorenal injury in rats. Nephron - Experimental Nephrology, 104(1), e6-e14. https://doi.org/10.1159/000093258