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The aim of our study was to determine the effect of recombinant human erythropoietin (rhEPO) on cyclosporine (CsA) nephrotoxicity. Twenty-six female Wistar rats were injected with 15 mg/kg subcutaneous CsA and intraperitoneal saline/rhEPO for 28 days. Four groups were formed: Group 1 (n = 5), a control group; Group 2 (n = 7), CsA + saline; Group 3 (n = 7), CsA + low dose (20 U/kg per day) rhEPO; Group 4 (n = 7), CsA + high dose (100 U/kg per day) rhEPO. Body weights, creatinine clearance, urinary protein/creatinine, hematocrit, serum creatinine levels, histopathological parameters, apoptosis and lipid peroxidation tests were compared between the three groups. Body weights and renal functions were similar in Groups 2, 3 and 4 rats but significantly lower than the values found for the control group at the end of the study. The hematocrit was significantly different between the four groups, showing a positive association with the strength of the injected rhEPO doses. Tubular and arteriolar damage was significantly lower in Groups 3 and 4 rats than in Group 2 rats, while chronic changes were similar between the three groups. TUNEL-positive cells and thiobabarbituric acid reacting substance (TBARS) levels were significantly higher in Group 2 rats, whereas superoxide dismutase levels were significantly lower in Group 2 rats than in those of the other three groups. Low or high dose rhEPO had no significant protective effects on body weight, renal functions, chronic fibrotic changes, but both doses reduced tubular and arteriolar changes, apoptotis and oxidative stress.

Recently, we have reported that erythropoietin (Epo) provides neuroprotection in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-induced neurotoxicity in vivo. In the present study, we investigated the effects of single Epo administration on brain antioxidant enzyme (superoxide dismutase (SOD) and glutathion peroxidase (GSHPx)) activities in this model in C57BL/6 mice. We found that MPTP treatment decreased GSHPx activity in both substantia nigra and striatum, and Epo restores nigral GSHPx activity decreased by MPTP. SOD enzyme activity was not significantly changed by MPTP and Epo treatment. Further, Epo stimulated astroglial GSHPx production in neonatal murine astroglial cell culture suggesting that the possible cell source for the stimulation of GSHPx activity by Epo in the MPTP-induced neurotoxicity model are astroglia. In conclusion, modulation of the astroglial antioxidant defense system might be one of the mechanisms by which Epo exerts a beneficial effect in MPTP-induced Parkinsonism.

Aim: In this study, we investigated whether interferon gamma (IFNy), lipopolysaccharides (LPS) and amyloid beta (AMYß), as toxic stimulator agents, and erythropoietin (EPO), as a neurotrophic agent, have an effect on the production of the following neurotrophic factors in the N9 murine microglia cell line: neurotrophin 3 (NT3), neurotrophin 4 (NT4), and brain-derived neurotrophic factor (BDNF). Materials and Methods: Microglial cells were incubated with 50 μg/ml AMYß, or 1μg/ml of LPS plus 100 U/ml recombinant murine IFNy, and/or one of three different concentrations (0.1, 1.0, and 5.0 U/ml) of recombinant mouse EPO for 24 h. Results: EPO 0.1 U/ml dose significantly increased NT4 levels compared to EPO 5.0 U/ml dose (P < 0.05). EPO, in all doses, and AMYß significantly induced NT4 secretion in microglias, while BDNF and NT3 were not changed by AMYß or EPO. LPS + IFNy alone did not change neurotrophic factor levels in any group. However, EPO with LPS and IFNy induced NT4 secretion, especially the 5.0 U/ml dose of EPO. Conclusions: NT4 secretion, which was markedly induced by exposure to both AMYß and EPO in N9 murine microglias, may be an important result for neuronal survival. These results suggest that inflammatory mechanisms in microglia may also involve the neuroprotective response of these cells; this may be a promising area of study of neurodegenerative processes. [ABSTRACT FROM AUTHOR]