Hemoglobin Oxidation Reactions in Stored Blood

Abstract

Hemoglobin (Hb) inside and outside the red blood cells (RBCs) undergoes constant transformation to an oxidized form in a process known as autoxidation. The ferrous heme iron (Fe2+) of the prosthetic group is spontaneously transformed into an oxidized ferric (Fe3+) form, but under oxidative stress conditions a higher oxidation ferryl heme (Fe4+) is also formed. Although Fe3+ is a non-functional form of Hb, the Fe4+ is also extremely reactive towards other biological molecules due to its high redox potential. The RBC contains an effective reductive machinery that maintains Hb in the functional form with little oxidation during its life span. The redox transformation of Hb occurs to a lesser extent in young RBCs; it may, however, have detrimental effects on the integrity of these cells during ex vivo storage or when RBCs are subjected to pathogen reduction processes. In this review, Hb oxidation reactions (“oxidative lesion”) will be described, including details of how these reactions might impact the clinical use of stored or processed blood for therapeutic purposes.

Supplementation with uric and ascorbic acid protects stored red blood cells through enhancement of non-enzymatic antioxidant activity and metabolic rewiring

“…Taken together, the beneficial effects of the supplementations on the extracellular and intra-cellular antioxidants provide a protection against the storage-related oxidative insults to RBCs. Well characterized phenotypes of storage lesion, including membrane lipid peroxidation [ 73 ], GSSG generation [ 74 ], oxidatively-induced lysis, and defected Hb binding to the membrane [ 5 , 75 , 76 ], were ameliorated in the presence of antioxidants. Both AA and UA protect lipids from detectable peroxidative damage and quench ROS, either alone [ 21 , 77 , 78 ] or in combination [ 79 ].…”

“…Moreover, the lower EV protein concentration, combined with the equal levels of protein stress-markers sorted in these EVs, could be informative regarding the extent of vesiculation in supplemented blood units. It is tempting to hypothesize that the minor Hb oxidation drives a lower microvesiculation rate [ 76 ] in the modified units. However, the lack of absolute enumeration, a limitation of the present study, cannot allow drawing broad conclusions about it.…”

The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

“…Having in mind that the enhanced blood units were characterized by decreased oxidative stress, this correlation might emerge only in low levels of oxidative lesions that can act as a statistical threshold. In any case, increased binding of denatured Hb to the membrane is a potent oxidation source, that contributes to protein defects, lipid peroxidation, and membrane/cytoskeleton integrity ( Alayash, 2022 ).…”

Oxidation reactions of cellular and acellular hemoglobins: Implications for human health

“…This also shed some light on the question of how HbS provides protection against malarial parasitic infection in SCD (46). Pseudoperoxidative activity of Hb and its potential impact on the integrity and long-term stability of blood stored in cold temperatures for 42 days was recently discussed (47). These reactions are collectively known as "oxidative lesion" which may impact clinical outcomes associated with the use of stored blood or pathogen inactivated blood for therapeutic purposes (47).…”