The effects of erythropoietin treatment on oxidative stress parameters in hippocampus of streptozotocin-induced diabetic rats

J Mršić-Pelčić1, K Pilipović1, G Pelčić0,2, D Vitezić1, G Župan1. 1School of Medicine Rijeka, Department of Pharmacology 51000, Croatia, 2Clinical Hospital Centre Rijeka, Clinics for Ophthalmology 51000, Croatia

Introduction: Neuronal damage is observed during untreated diabetes mellitus most likely due to oxidative injury and production of free radicals. Oxidative stress is important factor in pathogenesis of diabetes mellitus and its complications. Erythropoietin (Epo) is hematopoietic cytokine with significant neurotrophic and neuroprotective potential reported in various experimental models of brain damage. However, the mechanism of Epo protection is still unclear. The aim of our study was to examine the effect of Epo administration on oxidative stress parameters in hippocampus of streptozotocin (STZ) - induced diabetic rats. In the present study, we examined the effect of recombinant human Epo (rhEpo) administration on lipid peroxidation levels (TBARS) and antioxidant enzymes\' (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) activities in hippocampus of diabetic rats. Materials and methods: Diabetes mellitus was induced by intraperitoneal (i.p.) administration of single injection of streptozotocin (STZ) (65 mg/kg of body weight) to male Hannover-Wistar rats (150 mg). Animals were divided into several experimental groups, consisting of eight animals randomly assigned to each group. Five weeks after STZ injection, a part of diabetic animals received either rhEpo (40 µg/kg body weight), three times weekly for 5 weeks or vehicle. The levels of oxidative damage parameters, i.e. TBARS level, SOD and GSH-Px activities were determined spectrophotometrically in the hippocampus. All statistical analyses were performed using Statistica 8.0 software (StatSoft Inc., OK, USA). To investigate possible differences in biochemical parameters tested, analyses of variance (ANOVA) and Tukey HSD post hoc test were used. In all comparisons P < 0.05 was considered to indicate statistical significance. Results: Induction of diabetes mellitus significantly increased the level of lipid peroxidation as well as SOD activity while levels of GSH-Px activities were significantly decreased in comprison to non-diabetic animals. Epo treatment caused slight but not statistically significant decrease in TBARS level and SOD activities while the level of GSH-Px remained unaffected. Conclusions: Our results indicate that diabetes mellitus caused significant alterations in the levels and activities of oxidative stress parameters and that Epo treatment was not effective in preventing above mentioned alterations in our experimental model.