Scientific Publications by FDA Staff

Expert Opin Biol Ther 2007 May;7(5):665-75

First-generation blood substitutes: what have we learned? Biochemical and physiological perspectives.

Alayash AI, D'Agnillo F, Buehler PW

Alayash AI (reprint author), US FDA, CBER, Lab Biochem & vasc Biol, Div Hematol, NIH Campus,8800 Rockville Pike,Bldg 29,Room 112, Bethesda, MD 20892 USA US FDA, CBER, Lab Biochem & vasc Biol, Div Hematol, Bethesda, MD 20892 USA

Chemically modified or recombinant hemoglobin (Hb)-based oxygen carriers (HBOCs) have been developed as oxygen therapeutics or 'blood substitutes' for use in a variety of clinical settings. Oxidative and nitrosative reactions of acellular Hb can limit the effectiveness and compromise the safety of HBOCs. The reactions between Hb and biologically relevant redox active molecules may also perturb redox sensitive signaling pathways. In recent years, systematic in vitro and in vivo structural and functional evaluation of several HBOCs has been carried out and, in some cases, delineated the 'structural' origin of their toxicity. This enables potential protective strategies against Hb-mediated side reactions to be rationally suggested. Here the authors provide an overview of their research experiences, novel insights into the molecular basis of toxicities of these products and some lessons learned.