title: Effects of long-acting erythropoietin analog darbepoetin-α on adriamycin-induced chronic nephropathy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. zizomenna28@yahoo.com.
authors.forename: Abdelaziz M
authors.initials: AM
authors.lastname: Hussein
authors.affiliation: Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Eldosoky
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Handhle
authors.affiliation: Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Hanaa
authors.initials: H
authors.lastname: Elserougy
authors.affiliation: Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Sarhan
authors.affiliation: Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Sobh
authors.affiliation: Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mahmoud El
authors.initials: ME
authors.lastname: Hussiny
authors.affiliation: Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, Egypt.
authors.forename: Eman M
authors.initials: EM
authors.lastname: El Nashar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D000068256:Darbepoetin alfa / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D006397:Hematinics / Q000008:administration & dosage; D007678:Kidney Glomerulus / Q000187:drug effects / Q000648:ultrastructure*; D007684:Kidney Tubules / Q000187:drug effects / Q000648:ultrastructure*; D015227:Lipid Peroxidation; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D006397:Hematinics; D000068256:Darbepoetin alfa; D004317:Doxorubicin
keywords: Adriamycin; Caspase-3; Darbepoetin-α; Electron microscope; Kim-1; Podocytes; Sialoproteins