Antioxidative effects of erythropoietin.
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.
Katavetin
P
P
Division of Nephrology, Department of Medicine, Chulalongkorn University, Bangkok, Thailand. pkatavetin@yahoo.com
Tungsanga
K
K
Eiam-Ong
S
S
Nangaku
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019610:Cytoprotection; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D017467:Receptors, Erythropoietin / Q000502:physiology
D000975:Antioxidants; D017467:Receptors, Erythropoietin; D004921:Erythropoietin