Theoretical mechanistic basis of oxidants of methaemoglobin formation

The mechanism of oxidation or reduction using the electron method was investigated for (I) aniline; (II) nitrobenzene; (III) nitrate; (IV) sulphanilamide; (V) hydrogen peroxide; (VI) hydroxyl free radical; (VII) ferricyanide; (VIII) acotylphenylhydrazine; (IX) nitrite; (X) chlorate and (XI) hydroxylamine respectively. Substances (II), (III), (V), (Vf), (VII), (IX), (X) and (XI) evolved as oxidants, with (II), nitrobenzene and (X), chlorate as the most powerful oxidants (number of moles of HbFe(2+) (haemoglobin) of 6 reacting with 1.0 mole of the substance). Substances (I), (IV) and (VII) evolved as reductants of equal reducing power (number of moles of HbFe(3+) (methaemoglobin) of 4 reacting with 1.0 mole of the substance). Using the following equations, the impact of oxidants and reductants on glutathione (GSH) peroxidase, glutathione (GSSC) reductase and NADHmetHb reductase respectively on methaemoglobinaemia generation was investigated. 2HbFe(3+) + 2GSH -->(glutathione peroxidase) 2HbFe(2+) + GSSG + 2H(-) 2HbFe(2+) + GSSG + 2H(+) -->(glutathione reductase) 2HbFe(2+) + 2GSH 2HbFe(3+) + NADH -->(NADHmetHb reductase) 2HbFe(2+) + NAD(+) + H+ Redox potential change (Delta E'(o)) of 1.77, -1.77 and 1.86 volt and free energy change (Delta G(o)') of -81, 81 and -85.8 kcal/mol were calculated for GSH peroxidase, GSSG reductase and NADHmetHb reductase systems respectively. In sustained methaemoglobinaemia, these mechanisms predict low levels of NADHmetHb reductase and glutathione peroxidase respectively, but high levels of glutathione reductase in red blood cells on exposure to oxidants. The significance of these mechanisms was investigated in cord blood, neonatal, adult red blood cells and other biological systems. It was concluded that any reaction with a positive Delta E-o' and negative Delta G(o)' with the Fe3+: Fe2+ couple will indicate methaemoglobin oxidizing power. The effects on red blood cells and white blood cells were manifested in the biochemical toxicology of nitroso (PhN = 0), arylamine glucuronide (PhNHG) and arene imine respectively. (C) 2000 Harcourt Publishers Ltd.