Erythrocyte, plasma and substitute hemoglobins facing physiological oxidizing and reducing agents]

Oxidation of hemoglobin is constant and normal in red blood cells and in all biological media. The knowledge of the mechanisms which manage oxidation state is perhaps sufficient to treat acquired and some hereditary methemoglobinemia. But in case of transfusional treatment with hemoglobin based oxygen carrier (HBOC), some preclinical investigations on the oxidation of these products in vivo in plasma showed that our knowledge was not sufficient to understand and control all oxidations which could occur. This review analyses the literature on the different mechanisms in red blood cells and plasma by which hemoglobin autooxidizes and by which endogenous oxidizing agents or their precursors (nitric oxide, peroxynitrite, superoxide, hydrogen peroxide) could oxidize it. It shows the production of different radical or non-radical oxygen species during hemoglobin autooxidation and oxidation processes and the different physiological or accessory mechanisms that could prevent or reduce the various oxidizing states of hemoglobin (HbFe3+, HbFe4+) in blood. Plasma contains a few anti-oxidizing or reducing systems but it profits by antioxidizing and reducing activity from red blood cells. In blood, oxidation state of hemoglobin results from very complex phenomena and if the body struggles against methemoglobin formation to maintain oxygen transport, the oxidation of hemoglobin is sometimes useful to protect tissues against various and numerous endogenous radical or non-radical oxidizing agents. In blood, a balance between all these oxidizing and reducing mechanisms makes it possible to regulate circulating methemoglobin rate.