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

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.