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

In this study, a comparison between centrally and systemically administered erythropoietin (EPO) was performed on some kidney indices during hemorrhagic shock (HS) in male rats. Male Wistar rats were allocated into four experimental groups. 1) Sham; a guide cannula was inserted into the left lateral ventricle by stereotaxic surgery and other cannulas were placed into the left femoral artery and vein. 2) HS; stereotaxic surgery was done to insert a cannula in left lateral ventricle and after a 7-day recovery, hemorrhagic shock was induced by withdrawing fifty percent of blood volume and then resuscitation was performed with a mixture of Ringer’s lactate and the shed blood. 3) EPO-systemic; the procedure was the same as HS group except that animals received 300 IU/kg erythropoietin into the femoral vein immediately before resuscitation. 4) EPO-central; animals was treated to erythropoietin (2 IU/rat) into the left lateral ventricle before resuscitation. Arterial oxygen saturation (SaO 2 ) was measured during experiments. Urine was collected for biochemical studies and renal tissue samples were stored for ex-vivo indices assessments. 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 to the HS group. 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 with 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.