Pleiotropic and Renoprotective Effects of Erythropoietin Beta on Experimental Diabetic Nephropathy Model.

BACKGROUND: This study aimed at investigating the possible protective effect of erythropoietin beta on experimental diabetic nephropathy (DN) model in rats. METHODS: Sprague Dawley rats (n = 32) were allocated into 4 equal groups of 8 each, the control (Group C), diabetes (Group D), erythropoietin beta (Group E), and erythropoietin beta treated DN (Group E + D) groups. Streptozocin (65 mg/kg) was used to induce diabetes in 10-week old rats. Erythropoietin beta was given intraperitoneally at a dose of 500 IU/kg/3 days of a week for 12 weeks. Renal function parameters, intrarenal levels and activities of oxidative stress biomarkers, serum inflammatory parameters and kidney histology were determined. RESULTS: Group E + D had lower mean albumin-to-creatinine ratio (p < 0.001) as well as higher creatinine clearance (p = 0.035) than the diabetic rats (Group D). Intrarenal malondialdehyde levels were significantly lower (p = 0.004); glutathione (GSH) levels (p = 0.003), GSH peroxidase (p = 0.004) and superoxide dismutase (p < 0.005) activities of renal tissue were significantly higher in Group E + D than in Group D. The mean serum levels of interleukin-4 (p < 0.005), interleukin 1 beta (p = 0.012), interferon gamma (p = 0.018) and tumor necrosis factor alpha (p < 0.005) were significantly lower; serum levels of monocyte chemoattractant protein 1 (p = 0.018) was significantly higher in Group E + D when compared to Group D. The mean scores of tubulointerstitial inflammation (p = 0.004), tubular injury (p = 0.013) and interstitial fibrosis (p = 0.003) were also lower in Group E + D when compared to Group D. CONCLUSION: Our data seem to suggest a potential role of erythropoietin beta for reducing the progression of DN in an experimental rat model. This protective effect is, in part, attributable to the suppression of the inflammatory response and oxidative damage.

Effects of granulocyte-colony stimulating factor on the polymorphonuclear leukocyte activity and the course of sepsis in rats with experimental peritonitis.

PURPOSE: Polymorphonuclear leucocytes (PML) play an essential role in the host immune response to severe infections. The effects of granulocyte-colony stimulating factor (G-CSF) on the PML immune functions during serious abdominal infection and course of sepsis, and on the survival in rats with peritonitis are the main subjects of this study. METHODS: The first phase of the study was carried out on 30 Wistar-albino rats equally divided into three groups; Group 1 (control) sham laparotomy; Group 2 (peritonitis); and Group 3 (peritonitis+G-CSF) with fecal peritonitis created by a cecal puncture. At postoperative hours 3, 12, and 24, 0.5 ml normal saline was injected subcutaneously in groups 1 and 2, and 0.5 ml solution containing 50 microg/kg of G-CSF in group 3. The phagocytic and chemotactic activities of neutrophils and monocytes were evaluated by a flow cytometry analysis. The plasma lactate concentrations were assessed as a marker of tissue perfusion during sepsis. The second phase was a survival analysis, which was observed during 10 days on 20 rats equally divided into two groups; group 1 (peritonitis) and group 2 (peritonitis+G-CSF). 0.5 ml normal saline in group 1 and 50 microg/kg of G-CSF in group 2 was injected subcutaneously at the 3rd hour and twice daily. RESULTS: Both the neutrophil- (1.636 vs 2.236) and monocyte-related (1.789 vs 2.465) phagocytic activities significantly (P < 0.001) improved after the G-CSF administration in the rats with peritonitis. In addition, the G-CSF treatment significantly (P < 0.0014) improved the chemotactic activity (1.18 vs 2.75) of neutrophils, and partly supported (P < 0.0952) the chemotactic activity (1.69 vs 2.37) of monocytes. The plasma lactate level (1.86 vs 4.9 mmol/l) was significantly (P < 0.0001) increased after septic changes due to experimental peritonitis. On the other hand, the lactate concentration was significantly (P < 0.001) decreased (4.9 vs 2.63 mmol/l) after the G-CSF administration. The survival was 20% at the 4th day and 0 at the 6th day in peritonitis, and 90% at the 4th day (P = 0.0055) and 80% at the 6th day (P = 0.0007) days in the peritonitis+G-CSF groups. CONCLUSION: G-CSF enhances the immune functions of neutrophils and monocytes. The increased activities of these cells have a beneficial effect on the enhancement of the host immune response during severe infections. The improved immune function of PML due to the G-CSF treatment thus ameliorates the survival and the courses of sepsis, which is also defined by tissue perfusion and the cellular oxygen balance, which is affected by septic changes.