A Comparison of the Effect of Menadione, Methylene Blue and Ascorbic Acid on the Reduction of Methæmoglobin in vivo

Abstract

HEREDITARY methæmoglobinæmia, a rare disorder often associated with a deficiency in NADH-dependent ‘diaphorase’ activity¹, has been treated successfully with methylene blue (1–2 mg/kg intravenously) or ascorbic acid (200–500 mg/day orally)². Methylene blue probably effects the reduction of methæmoglobin by activating the NADPH-dependent methæmoglobin reductase that has been isolated, from human erythrocytes by Kiese et al.³ and by Huennekens et al.⁴. By serving as electron carriers between NADPH and the methæmoglobin reductase, methylene blue and other artificial electron carriers increase the activity of the hexose monophosphate shunt pathway of glucose metabolism⁵ and facilitate the reduction of methæmoglobin to hæmoglobin. This NADPH-dependent methæmoglobin reductase system is a reserve mechanism for the reduction of methæmoglobin, for the NADH-dependent ‘diaphorase’ system appears to be the physiologically important pathway in normal human erythrocytes. Ascorbic acid can reduce methæmoglobin to hæmoglobin slowly both in vivo and in vitro, probably through a direct effect on the methæmoglobin².