Oxygen therapeutics: can we tame haemoglobin?
Chemically modified or genetically engineered haemoglobins (Hbs) developed as oxygen therapeutics (often termed 'blood substitutes') are designed to correct oxygen deficit due to ischaemia in a variety of clinical settings. These modifications are intended to stabilize Hb outside its natural environment--red blood cells--in a functional tetrameric and/or polymeric form. Uncontrolled haem-mediated oxidative reactions of cell-free Hb and its reactions with various oxidant/antioxidant and cell signalling systems have emerged as an important pathway of toxicity. Current protective strategies designed to produce safe Hb-based products are focused on controlling or suppressing the 'radical' nature of Hb while retaining its oxygen-carrying function.
Alayash
Abdu I
AI
Laboratory of Biochemistry, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, National Institutes of Health, Bethesda, Maryland 20892, USA. alayash@cber.fda.gov
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001802:Blood Substitutes / Q000009:adverse effects / Q000378:metabolism*; D023281:Genomics; D006454:Hemoglobins / Q000235:genetics* / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D010084:Oxidation-Reduction; D010100:Oxygen / Q000627:therapeutic use*
D000975:Antioxidants; D001802:Blood Substitutes; D006454:Hemoglobins; D010100:Oxygen