Clinical & Medical Biochemistry

Oxidative Reactions and Toxicity of Hemoglobin and its Oxidative Pathway in Blood

Edward Pope^* Department of Biochemistry, The University of Western Australia, Perth, Australia
^*Correspondence: Edward Pope, Department of Biochemistry, The University of Western Australia, Perth, Australia, Email:

Received: 03-Mar-2023, Manuscript No. CMBO-23-20917; Editor assigned: 06-Mar-2023, Pre QC No. CMBO-23-20917 (PQ); Reviewed: 20-Mar-2023, QC No. CMBO-23-20917; Revised: 27-Mar-2023, Manuscript No. CMBO-23-20917 (R); Published: 03-Apr-2023, DOI: 10.35841/2471-2663.23.9.160

Description

Hemoglobin (abbreviated Hb or Hgb in British English) is an iron-containing oxygen-transport metalloprotein found in nearly all vertebrate red blood cells (erythrocytes) and some invertebrate organs. Blood hemoglobin transports oxygen from the lungs and gills to the rest of the body (i.e. tissues). The oxygen is released there, allowing aerobic respiration to occur and provide energy for an organism's metabolic functions. A healthy person's blood contains 12 gms to 20 gms of hemoglobin per 100 mL. Reactive Oxygen Species (ROS) can produce hydroxyl radicals from Hb, which was identified as a biological Fenton reagent. These hydroxyl radicals are produced when the iron in Hb reacts with hydrogen peroxide (H₂O₂). Many acellular Hb solutions that were created as blood replacements and had various sources and chemistries have been thoroughly examined for the pseudoperoxidative activity of Hb. This reaction is catalyzed by the catalyst H₂O₂ and consists of three distinct steps: the initial oxidation of HbFe₂ (oxy) to ferryl (HbFe⁴⁺), the auto reduction of the ferryl intermediate to ferric (HbFe³⁺), and the reaction of metHb with a second molecule of H₂O₂ to regenerate the ferryl intermediate. Ferryl Hb was discovered in a number of ex vivo and in vivo model systems, including carotid atherosclerotic lesions, mice blood, blood from Sickle Cell Disease (SCD) patients, and blood from SCD patients who had malaria.

The ferryl Hb's redox reactivities have been linked to particular cellular, and in some cases subcellular, damage. SCD is a special model system that made it possible to carefully examine Hb's pseudoperoxidase activity. When exposed to oxidants, Sickle Cell Hemoglobin (HbS) underwent significant alterations, with ferryl Hb being more harmful to organelles and tissues because it remained in solutions longer than ferryl HbA. Throughout the typical lifespan of RBCs, around 1%-3% of Hb is converted into an oxidised non-functional (ferric/met) state. MetHb reductase quickly reverts metHb to ferrous/oxyHb in the presence of NADH. MetHb levels rise because metHb reductase's activity decreases during RBC storage, preventing it from being transformed back into oxyHb. The rise in Hb oxidation during RBC storage may also be brought on by a decline in their antioxidant ability, which can cause membrane lipids and proteins to oxidise and degrade, ultimately causing irreparable membrane damage. During storage, a small percentage of red cells lyse spontaneously, and vesicles containing both lipids and Hb from intact red cells are shed into the supernatant plasma. In a guinea pig model with a vascular disease phenotype, the effects of RBC exchange transfusion dosages (1, 3, and 9 units), storage period (14 days), and mortality were recently assessed. The lack of ascorbate synthesis pathways in guinea pigs, a crucial antioxidant mechanism known to regulate Hb oxidation processes, makes them similar to humans.

A higher rate of Hb oxidation occurs when RBCs are stored ex vivo, antioxidant activity is reduced, the storage medium contains high quantities of glucose, and molecular oxygen is present. For up to 6 weeks, RBCs were stored in units of citratephosphate- dextrose-adenine storage solution. During this time, the RBCs showed signs of oxidative damage, including the attachment of denatured Hb—likely hemichromes to membrane phospholipids and cytoskeleton proteins like spectrin. Microvesicles also contained traces of denatured Hb. Recent efforts have been made to reduce oxidative damage. Human plasma and tirilazad mesylate were discovered to protect stored human RBCs from gamma irradiation-induced oxidative damage. Tirilazad mesylate, a 21-aminosteroid that is nonglucocorticoid, reduces lipid peroxidation by a combination of radical scavenging and membrane-stabilizing characteristics. It was discovered that normal human plasma was effective at protecting irradiated RBCs from oxidative damage. Additionally, the synthetic antioxidant trilazad mesylate, which scavenges ROS, proved effective at protecting red cells from oxidative damage. The role of Hb's redox modification of nitric oxide (NO) has spilled over into blood transfusion practices as a potential therapeutic technique to reverse the storage lesion. S-Nitrosylation (SNO) of Cys93 and nitrite reductase enzymatic activity of Hb resulted in Hb/NO complexes/intermediates that can release NO and counteract biochemical alterations associated with RBC ageing. NO binds to Hb at over 600 times the rate of its natural companion, oxygen. The most immediate consequence of this process is metHb-NO complexes, which can be redox cycled by Hb with little or no protein degradation. NO release from Hb within RBCs is both kinetically and physiologically implausible.