Antioxidative effects of erythropoietin

Abstract

Erythropoietin (EPO) has been shown to exert cytoprotective effects on erythroid progenitor cells as well as various non-erythroid cells. Experimental studies have demonstrated the renoprotective effects of EPO in various acute and chronic renal injury models. These protective effects have been largely attributed to antiapoptotic signalings of EPO. However, injured cells undergoing apoptosis are generally too severely damaged to function properly. Therefore, simply corrupting apoptotic pathway is unlikely to be an effective strategy, because the remaining damaged cells may not function appropriately, or they may eventually undergo necrotic cell death. Recent evidences suggest that EPO also provides cytoprotection by ameliorating oxidative stress, the principal cellular insult. EPO may exert its antioxidative effects directly by exploiting intracellular antioxidative mechanisms such as heme oxygenase-1 and glutathione peroxidase. In addition, EPO may act indirectly by inducing iron depletion and thereby inhibiting iron-dependent oxidative injury. Increasing red blood cells by EPO may also indirectly reduce cellular oxidative stress, as red blood cells are loaded with a substantial amount of antioxidative enzymes. Further investigation regarding the mechanisms of cellular antioxidative responses to EPO would provide a better insight to cytoprotective action of EPO, and would support the development of better cytoprotective drugs in the near future.

The Ovario-Protective Effect of Erythropoietin against Oxidative Damage Associated with Reperfusion Following Ovarian Torsion in Rat

“…EPO is a tissue-protective cytokine this seems to be true for all organs expressing the EPO receptor. The antioxidative effects of EPO have also demonstrated by Katavetin et al (2007). According to these authors, the antioxidative properties of EPO may arise from its direct effect on intracellular antioxidative mechanisms such as heme oxygenase-1 and glutathione peroxidase.…”

Discovery and basic pharmacology of erythropoiesis-stimulating agents (ESAs), including the hyperglycosylated ESA, darbepoetin alfa: an update of the rationale and clinical impact

“…One possibility is that the increased iron metabolism needed to support ESA-induced erythropoiesis may reduce oxidative stress [34]. Alternatively, increases in oxygen delivery at elevated hematocrits or changes in heart rate or blood hemodynamics may also explain the benefit of ESAs in certain animal studies.…”

Erythropoiesis-stimulating agent slows the progression of chronic kidney disease: a possibility of a direct action of erythropoietin

“…Such mechanisms are suggested to be involved in the renoprotective effects of ESA in acute kidney injury and CKD. 22,23 The third possible mechanism is the inhibitory effect of EPO on inflammation and fibrosis. Attenuation of interstitial inflammation and fibrosis by EPO therapy has been reported in the models of chronic cyclosporine nephropathy, 24 ureteral obstruction, [25][26][27] and Thy-1 glomerulonephritis.…”