Methemoglobin—It's not just blue: A concise review

Abstract

Hemoglobin has functions besides carrying oxygen to the tissues, and regulates vascular tone and inflammation via a redox couple with methemoglobin. Hemoglobin has iron in the reduced valance Fe(II) and methemoglobin has iron in the oxidized valance Fe (III), with a free energy capable of producing water from oxygen. In generating methemoglobin the couple functions as a nitrite reductase. The degree of oxidation of hemoglobin senses the oxygen level in the blood and uses its ability to produce nitric oxide from nitrite to control vascular tone, increasing blood flood when the proportion of oxygenated hemoglobin falls. Additional cardiovascular damage is produced by methemoglobin mediated oxidation of light density lipoproteins, accelerating arteriosclerosis. In addition, the release of heme from methemoglobin is an important factor in inflammation. These physiologic functions are paralleled by the well-described role in the oxidation of various drugs resulting in methemoglobinemia. Am. J. Hematol. 82:134-144, 2007. V V C 2006 Wiley-Liss, Inc.

Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage

“…High levels of methemoglobin have been reported in CSF after IVH. 22,23 We will continue to pursue the potential role of Fe 2 þ in IVH-induced brain injury in other studies, but this is hampered by a lack of specific chelators available for ferrous iron.…”

Reassessing the risk of hemodilutional anemia: Some new pieces to an old puzzle

“…92,96 Methylene blue acts by restricting NO bioavailability by three mechanisms: 1) inhibition of NOS; 2) direct scavenging of NO; and 3) inhibiting the action of downstream soluble guanylate cyclase ( Figure 6). 100 Thus, methylene blue may improve blood pressure at the expense of impairing NO-mediated tissue perfusion and oxygen delivery. Hemodilution is common during cardiac surgery and is associated with NOS-dependent increases in cerebral blood flow 89,101 and increased expression of brain nNOS in experimental models.…”

L-arginine, a nitric oxide precursor, reduces dapsone-induced methemoglobinemia in rats

“…The NADPH system reduces methemoglobin to hemoglobin through the enzyme NADPH-methemoglobin reductase and contributes to 5% of methemoglobin reduction. Finally, the conversion of reduced glutathione to glutathione influences methemoglobin levels by reducing oxidizing agents (Evelo et al, 1998;Ward, McCarthy, 1998;Umbreit, 2007).…”

“…The NADPH system reduces methemoglobin to hemoglobin through the enzyme NADPH-methemoglobin reductase and contributes to 5% of methemoglobin reduction. Finally, the conversion of reduced glutathione to glutathione influences methemoglobin levels by reducing oxidizing agents (Evelo et al, 1998;Ward, McCarthy, 1998;Umbreit, 2007).The standard treatment for methemoglobinemia includes infusion with methylene blue, whose action depends on the availability of NADPH within the erythrocytes. This therapy requires glucose-6-phosphate dehydrogenase (G6PD) optimal activity to produce sufficient amounts of NADPH.…”