Proposed Mechanism of Nitrite-Induced Methemoglobinemia

---

V. Yu. Titov^* and Yu. M. Petrenko

Russian State Medical University, ul. Ostrovityanova 1, 117437 Moscow, Russia; E-mail: nmc@tsinet.ru

^* To whom correspondence should be addressed.

Received May 18, 2004; Revision received July 5, 2004

---

A scheme of development of nitrite-induced oxyhemoglobin oxidation in erythrocytes based on the analysis of experimental data is proposed. It was found that, contrary to widespread opinion, direct oxidative-reductive interaction between hemoglobin and nitrite is absent or negligible under physiological conditions. The driving stage of this process is methemoglobin-catalyzed peroxidase oxidation of nitrite. The product of the oxidation (presumably NO₂^·) directly oxidizes oxyhemoglobin to methemoglobin-peroxide complex without hydrogen peroxide release into the environment. The oxidant itself is reduced to nitrite or oxidized to nitrate as a result of interaction with another NO₂^· molecule. Thus, the stoichiometry of the process depends on the ratio of rates of these two reactions. Substances that are able to compete with nitrite for peroxidase and therefore to prevent the nitrite oxidation effectively protect hemoglobin from oxidation. Catalase is not able to destroy methemoglobin-peroxide complexes, but it can prevent their production in the course of interaction of methemoglobin and free peroxide by destroying the latter.

---

KEY WORDS: nitrite, oxyhemoglobin, methemoglobinemia

---