Abdelaziz M Hussein1, Mohamed Eldosoky2, Ahmed Handhle3, Hanaa Elserougy2, Mohamed Sarhan2, Mohamed A Sobh4, Mahmoud El Hussiny4, Eman M El Nashar5. 1. Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. zizomenna28@yahoo.com. 2. Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 3. Medical Biochemistry Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 4. Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 5. Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, Egypt.
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.
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.
Entities:
Keywords:
Adriamycin; Caspase-3; Darbepoetin-α; Electron microscope; Kim-1; Podocytes; Sialoproteins
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