Comparison of the oxidative reactivity of recombinant fetal and adult human hemoglobin: implications for the design of hemoglobin-based oxygen carriers

Simons, M, Gretton, Svetlana, Silkstone, G.A, Rajagopal, B.S, Allen-baume, Victoria, Syrett, N, Shaik, T, Leiva-Eriksson, N, Ronda, L, Mozzarelli, A, Straider, M.B., Alayash, A.I., Reeder, B.J and Cooper, C.E. (2018) Comparison of the oxidative reactivity of recombinant fetal and adult human hemoglobin: implications for the design of hemoglobin-based oxygen carriers. Bioscience reports, 38 (4). ISSN 1573-4935

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Abstract

Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been engineered to replace or augment the oxygen carrying capacity of erythrocytes. However, clinical results have generally been disappointing, in part due to the intrinsic oxidative toxicity of Hb. The most common HBOC starting material is adult human or bovine Hb. However, it has been suggested that fetal Hb may offer advantages due to decreased oxidative reactivity. Large-scale manufacturing of HBOC will likely and ultimately require recombinant sources of human proteins. We, therefore, directly compared the functional properties and oxidative reactivity of recombinant fetal (rHbF) and recombinant adult (rHbA) Hb. rHbA and rHbF produced similar yields of purified functional protein. No differences were seen in the two proteins in: autoxidation rate; the rate of hydrogen peroxide reaction; NO scavenging dioxygenase activity; and the NO producing nitrite reductase activity. The rHbF protein was: less damaged by low levels of hydrogen peroxide; less damaging when added to human umbilical vein endothelial cells (HUVEC) in the ferric form; and had a slower rate of intrinsic heme loss. The rHbA protein was: more readily reducible by plasma antioxidants such as ascorbate in both the reactive ferryl and ferric states; less readily damaged by lipid peroxides; and less damaging to phosphatidylcholine liposomes. In conclusion in terms of oxidative reactivity, there are advantages and disadvantages to the use of rHbA or rHbF as the basis for an effective HBOC.

Keywords: adult, blood substitute, fetal, hemoglobin, oxidative stress, oxygen carrier

Item Type: Article
Uncontrolled Keywords: hemoglobin, artificial blood, blood types
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Health & Science > Department of Science & Technology
Depositing User: Svetlana Gretton
Date Deposited: 06 Feb 2020 10:31
Last Modified: 06 Feb 2020 10:31
URI: http://oars.uos.ac.uk/id/eprint/1148

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