Scientific Publications by FDA Staff

Nat Rev Drug Discov 2004 Feb;3(2):152-9

Oxygen therapeutics: Can we tame haemoglobin?

Alayash AI

Alayash AI, US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, 8800 Rockville Pike,NIH Bldg 29,Room 112, Bethesda, MD 20892 USA US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA

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.