A comparison between centrally and systemically administered erythropoietin on kidney protection in a model of fixed-volume hemorrhagic shock in male rats

Abstract

Background: In this study, a comparison between centrally and systemically administered erythropoietin (EPO) was performed on nephroprotection during hemorrhagic shock (HS) in male rats.

Methods: Male rats were allocated into four experimental groups. (1) Sham; a guide cannula was inserted into the left lateral ventricle and other cannulas were placed into the left femoral artery and vein. (2) HS; stereotaxic surgery was done to insert a cannula in the left lateral ventricle and after a 7-day recovery; hemorrhagic shock and resuscitation were performed. (3) EPO-systemic; the procedure was the same as the HS group except that animals received 300 IU/kg erythropoietin into the femoral vein immediately before resuscitation. (4) EPO-central; animals was treated with erythropoietin (2 IU/rat) into the left lateral ventricle before resuscitation. Arterial oxygen saturation (SaO₂) was measured during experiments. Urine and renal tissue samples were stored for ex-vivo indices assessments.

Results: Erythropoietin (systemically/centrally administered) significantly improved SaO_2, renal functional and oxidative stress parameters and decreased renal inflammatory (TNF-α and IL-6) mRNA expression compared to the HS group. EPO-treated groups showed a decrease in active form of caspase-3 protein level and an increase in autophagy activity in comparison with the HS group.

Conclusion: Considering the fact that the effective dose of systemic EPO (300 IU/kg) was roughly 50 times higher than that of central administration (2 IU/rat), centrally administered EPO was accompanied by more advantageous consequences than systemic way. EPO is likely to act as a neuro-modulator or neuro-mediator in the central protection of organs including the kidneys.

Keywords: Erythropoietin; Hemorrhagic shock; Inflammation; Intracerebroventricular infusion; Stereotaxic technique.