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Editorial
. 2008 Jul;295(1):H4-7.
doi: 10.1152/ajpheart.00499.2008. Epub 2008 May 23.

The proverbial chicken or the egg? Dissection of the role of cell-free hemoglobin versus reactive oxygen species in sickle cell pathophysiology

Megan L Krajewski, Lewis L Hsu, Mark T Gladwin
Editorial

The proverbial chicken or the egg? Dissection of the role of cell-free hemoglobin versus reactive oxygen species in sickle cell pathophysiology

Megan L Krajewski et al. Am J Physiol Heart Circ Physiol. 2008 Jul.
No abstract available

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Figures

Fig. 1.
Fig. 1.
A vicious cycle of hemolysis, nitric oxide (NO) resistance, and oxidant stress, with interruption by arginine repletion. In sickle cell disease, hemoglobin S (HbS) leads to red blood cell (RBC) hemolysis, decreased NO bioavailability, and oxidant stress. Intravascular hemolysis releases cell-free hemoglobin into the plasma compartment, contributing directly to both impaired NO bioavailability and oxidant stress. Hemolysis alters NO homeostasis through scavenging of NO by cell-free hemoglobin and consumption of arginine by arginase released from hemolyzed RBCs. Hemolysis drives oxidant stress through free hemoglobin-mediated peroxidase, autooxidation, and Fenton chemistries, producing nitrogen dioxide and tyrosine nitration. NO resistance is aggravated by enzymatic (xanthine oxidase and NADPH oxidase) production of superoxide, which scavenges NO. Oxidant stress perpetuates the cycle by rendering RBCs more susceptible to damage and hemolysis. Remarkably, arginine supplementation appears to target this triad of pathology by increasing NO formation, reducing hemolysis, and reducing oxidant stress. NOS, NO synthase.
See this image and copyright information in PMC

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