Redox concerns in the use of acellular hemoglobin-based therapeutic oxygen carriers: the role of plasma components.
Within the past decade, most research efforts in the red blood cell substitute area have revolved about the development of acellular hemoglobin-based oxygen carriers (HBOC) as clinical replacements and/or augmentation of human blood's carrying and delivery function. A major requirement for all HBOC is the maintenance of the heme-Fe+2 in this reduced state for normal physiological behavior. Oxidation of hemoglobin results in the formation of methemoglobin (heme-Fe+3). MetHb is unable to bind oxygen thus effectively lowering the carrying capacity of the Hb-based substitute. In addition, met Hb gives rise to free radicals that have the potential to cause endothelial and surrounding tissue damage. Results of this study suggest that the normal endogenous reducing agents of human plasma have the capacity to provide redox protection and stability to specific acellular-types of HBOC. The effectiveness of these reducing agents may be related to the formal reduction potential of the HBOC being considered. The choice of buffer for HBOC storage is critical and specific to the HBOC product.
Harrington
J P
JP
Department of Chemistry, University of South Alabama, Mobile, AL 36688, USA. jharring@jaguar1.usouthal.edu
Gonzalez
Y
Y
Hirsch
R E
RE
D000328:Adult; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000031:analogs & derivatives* / Q000737:chemistry*; D001639:Bicarbonates / Q000494:pharmacology; D001802:Blood Substitutes / Q000737:chemistry*; D001826:Body Fluids / Q000737:chemistry*; D002021:Buffers; D005609:Free Radicals; D005978:Glutathione / Q000494:pharmacology*; D006531:HEPES / Q000494:pharmacology; D006418:Heme / Q000737:chemistry; D006441:Hemoglobin A / Q000737:chemistry / Q000187:drug effects; D006454:Hemoglobins / Q000737:chemistry* / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry; D008706:Methemoglobin / Q000737:chemistry; D009243:NAD / Q000494:pharmacology*; D009835:Oligochaeta / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D010108:Oxyhemoglobins / Q000737:chemistry* / Q000187:drug effects; D010710:Phosphates / Q000494:pharmacology; D019163:Reducing Agents / Q000494:pharmacology*; D014325:Tromethamine / Q000494:pharmacology
D001639:Bicarbonates; D001802:Blood Substitutes; D002021:Buffers; D005609:Free Radicals; D006454:Hemoglobins; D010108:Oxyhemoglobins; D010710:Phosphates; D019163:Reducing Agents; C053936:hemoglobin XL99alpha; D014325:Tromethamine; D009243:NAD; C091201:Tribonate; D006418:Heme; D008706:Methemoglobin; D006441:Hemoglobin A; D007501:Iron; D005978:Glutathione; D001205:Ascorbic Acid; D001241:Aspirin; D006531:HEPES; D010100:Oxygen; C018279:sodium phosphate