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Native circulating erythrocytes (not having undergone CPB) have a high concentration of ascorbic acid, which works as a reducing agent together with glutathione (not with V-B12) to neutralize reactive oxygen species (peroxides) generated by heme cofactors.7,8 Reduced V-B12 may be a viable separate drug for the treatment of CO poisoning, which manifests with vasoplegia, although it should be noted that only animal studies have been performed to explore this.7,8 Cobalt in hydroxocobalamin and iron in heme Heme proteins with iron in the +2 oxidation state (i.e., Hb, myoglobin, cytochrome c oxidase) have near diffusion-limited rate constants for NO coordination, as well as extraordinarily small dissociation constants (e.g., 10 10 10 11 M) for the NO adducts.54 Similar to the reaction of V-B12 with NO, Hb binding NO is nearly irreversible in the body

10.1016/j.redox.2016.10.001 27 El-HassanH.AnwarK.Macanas-PirardP.CrabtreeM.ChowS

It does not cause the fluid retention that strains the cardiovascular system

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