Differential Effects of Low-Dose Erythropoietin in Rat Model of Diabetic Nephropathy

Abstract

Background. Previous reports on the renoprotective effect of erythropoietin (EPO) in the setting of chronic kidney disease (CKD) have yielded conflicting results. The aim of this study is to clarify the effect of low, non-hematopoietic dose of EPO on the evolution of diabetic nephropathy (DN) in rat model. Methods. Low dose of recombinant human EPO (150 U/kg, s.c. three times/week) was given to streptozotocin (STZ)-induced diabetic rats in two schedules; in the first one, EPO was given from day 2 after STZ injection till the end of the study (28 weeks) as prophylactic treatment; and in the other schedule EPO was given after development of DN (last 8 weeks) as therapeutic treatment. Albuminuria, blood pressure, creatinine clearance, renal venous oxygen tension (vPO2), plasma EPO, hematocrit and renal histopathology were assessed. Results. Unexpectedly, 28 weeks administration of EPO to diabetic rats led to aggravation of albuminuria and worsening of histopathological damage in spite of partial correction of renal hypoxia. Contrary to this, terminal 8 weeks EPO therapy of DN reduced albuminuria and demonstrated some favorable effects on biochemical changes and histologic picture. Conclusion. Low dose EPO exerted differential effects in rat model of DN according to treatment duration. In addition, findings of the present study warrants further investigations of the exact renoprotective role of EPO in diabetic patients with CKD who receive EPO therapy for long periods.

Pentosan polysulfate exerts anti‐inflammatory effect and halts albuminuria progression in diabetic nephropathy: Role of combined losartan

“…All kidney tissues were stained with hematoxylin & eosin (H&E) and periodic acid Schiff (PAS). Changes in kidney structure were analyzed to assess the severity of the morphologic changes (glomerulosclerosis, interstitial inflammation, interstitial fibrosis tubular atrophy “IFTA,” and vascular lesions) and then each type of lesion was graded semiquantitatively as described previously [5].…”

“…Previously, DN was described as a glomerular disease; however, additional evidence has emerged to design a new pathological classification that involves tubules, interstitium, and/or the renal vasculature [4]. All these changes could be reproduced and quantified in animal models [5]. Despite the favorable effects of the current treatment of DN that are based mainly on adequate glycemic control and renin angiotensin system (RAS) blockade, albuminuria and the progression of renal disease are not completely prevented.…”

The impact of ginger and curcumin on diabetic nephropathy induced by streptozotocin in rats

“…Neutral buffered formalin (10%) was perfused into the left kidneys of all rats, which were then processed into 5-mm paraffin sections for histological examination. Hematoxylin and eosin (H & E), Masson, periodic acid-Schiff (PAS), and immunostaining renal sections against NF-κB were used to stain all kidney tissues [6]. NF-κB expression was assessed through the immunostaining of deparaffinized samples slides using polyclonal NF-κB antibody (sc-59103) from Santa Cruz Biotechnology Inc., CA, USA) diluted 1:50.…”

“…Studies investigating the potential benefits of nutritional antioxidants in diabetes patients have been conducted. Additionally, there's a growing demand for herbal medications derived from medicinal plants [6].…”