Hydrogen peroxide-induced cell and tissue injury: protective effects of Mn2+.

Recent evidence indicates that under in vitro conditions, superoxide anion and hydrogen peroxide (H2O2) are unstable in the presence of manganese ion (Mn2+). The current studies show that in the presence of Mn2+, H2O2-mediated injury of endothelial cells is greatly attenuated. A source of bicarbonate ion and amino acid is required for Mn2+ to exert its protective effects. Injury by phorbol ester-activated neutrophils is also attenuated under the same conditions. EDTA reverses the protective effects. Acute lung injury produced in vivo in rats by intratracheal instillation of glucose-glucose oxidase is almost completely blocked in rats treated with Mn2+ and glycine. Conversely, treatment of rats with EDTA, a chelator of Mn2+, markedly accentuates lung injury caused by glucose-glucose oxidase. These data are consistent with the findings of others that Mn2+ can facilitate direct oxidation of amino acids with concomitant H2O2 disproportionation. This could form the basis of a new therapeutic approach against oxygen radical-mediated tissue injury.