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Effects of long-acting erythropoietin analog darbepoetin-α on adriamycin-induced chronic nephropathy

  • Nephrology - Original Paper
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Abstract

Objectives

To study the effects of darbepoetin-α (DPO-α) (erythropoietin analog) on adriamycin (ADR)-induced chronic nephropathy in rats.

Methods

Sixty-nine male Sprague-Dawley rats divided into 3 groups (23 rats each): negative control group: normal rats received saline as a vehicle; positive control (ADR) group: rats received 2 iv injection of ADR via penile vein at 14-day interval without treatment; and DPO-α group: as ADR group but rats received sc DPO-α (0.3 μg/kg bw) once weekly for 12 weeks. By the end of experiment hemoglobin (Hb) content, serum creatinine, BUN, albumin, triglycerides and cholesterol, urinary protein excretion and kidney injury molecule-1 (KIM-1). GSH, malondialdehyde, caspase-3 expression histopathological and electron microscopic examinations for kidney tissues were done.

Results

DPO-α significantly improved the animal survival rate and body weight, Hb, serum BUN, triglycerides, cholesterol, and albumin and urinary protein excretion and KIM-1 in urine. Also, administration of DPO-α improved the morphological damage in glomeruli and renal tubules as well as caspase-3 expression and markers of oxidative stress in kidney tissues.

Conclusion

Administration of DPO-α alleviates ADR nephropathy and this might due to improvement of Hb content, hyperlipidemia, enhancement of endogenous antioxidants, reduction of apoptosis and tubulointerstitial injury and maintaining the integrity of glomerular membrane.

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Acknowledgments

We acknowledge Dr Azza El Hadidy, professor of Histology and Cell Biology, Mansoura Faculty of Medicine for her help in histopathological examination.

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Authors and Affiliations

  1. Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Abdelaziz M. Hussein, Mohamed Eldosoky, Hanaa Elserougy & Mohamed Sarhan

  2. Medical Biochemistry Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Ahmed Handhle

  3. Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Mohamed A. Sobh & Mahmoud El Hussiny

  4. Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, Egypt

    Eman M. El Nashar

Authors
  1. Abdelaziz M. Hussein
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  2. Mohamed Eldosoky
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  3. Ahmed Handhle
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  5. Mohamed Sarhan
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Correspondence to Abdelaziz M. Hussein.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Hussein, A.M., Eldosoky, M., Handhle, A. et al. Effects of long-acting erythropoietin analog darbepoetin-α on adriamycin-induced chronic nephropathy. Int Urol Nephrol 48, 287–297 (2016). https://doi.org/10.1007/s11255-015-1171-1

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  • DOI: https://doi.org/10.1007/s11255-015-1171-1

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