Abstract
Previous generations of hemoglobin (Hb)-based oxygen carriers (HBOCs) have been plagued by key biophysical limitations that result in severe side-effects once transfused in vivo, including protein instability, high heme oxidation rates, and nitric oxide (NO) scavenging. All of these problems emerge after mammalian Hbs are removed from red blood cells (RBCs) and used for HBOC synthesis/formulation. Therefore, extracellular Hbs (erythrocruorins) from organisms which lack RBCs might serve as better HBOCs. This review focuses on the erythrocruorin of Lumbricus terrestris (LtEc), which has been shown to be extremely stable, resistant to oxidation, and may interact with NO differently than mammalian Hbs. All of these beneficial properties show that LtEc is a promising new HBOC which warrants further investigation.
Highlights
Previous generations of hemoglobin (Hb)-based oxygen carriers (HBOCs) have been plagued by key biophysical limitations that result in severe side-effects once transfused in vivo, including protein instability, high heme oxidation rates, and nitric oxide (NO) scavenging
The major problems associated with these HBOCs (instability, oxidative stress, and nitric oxide (NO) scavenging) can be directly attributed to removing Hb from the protective environment within the red blood cell (RBC)
Since mammalian Hbs purified from RBCs are burdened with so many problems, extracellular Hbs from other organisms may be better suited for use in HBOC development
Summary
As of 2011, the only hemoglobin (Hb) based oxygen carriers (HBOCs) that have entered phase III clinical trials are polymerized human [1,2,3,4] and bovine [5,6,7,8] Hb (PolyHb) as well as poly(ethylene glycol) surface-conjugated human hemoglobin (MP4, Sangart Inc., San Diego, CA, USA) [9,10,11,12]. Since mammalian Hbs purified from RBCs are burdened with so many problems, extracellular Hbs from other organisms may be better suited for use in HBOC development. This special class of Hbs, known as erythrocruorins (Ecs), are found in organisms which lack RBCs (most annelids [20], some mollusks [21] and insects [22]).
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