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This pro-oxidant environment has been explained by a number of erythroid and non-erythroid mechanisms, including (1) HbS auto-oxidation, (2) heme and iron release, (3) increased activity of endothelial xanthine oxidase (XO) and NADPH oxidase, (4) decreased NO· bioavailability, and (5) erythroid mitochondrial retention [80]
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