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

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Abstract

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 snow 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.

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References

  1. Cheton, P. B. L., andF. S. Archibald. 1988. Manganous complexes and the generation and scavenging of hydroxyl free radicals.Free Radical Biol. Med. 5:325–330.

    Google Scholar 

  2. Gutteridge, J. M. C., andJ. V. Bannister. 1986. Copper + zinc and manganese Superoxide dismutase inhibit deoxyribose degradation by the superoxide-driven fenton reaction at two different stages.Biochem. J. 234:225–231.

    Google Scholar 

  3. Stadtman, E. S., B. S. Berlett, andP. B. Chock. 1990. Manganese-dependent disproportionation of hydrogen peroxide in bicarbonate buffer.Proc. Natl. Acad. Sci. U.S.A. 87:384–390.

    Google Scholar 

  4. Berlett, B. S., P. B. Chock, M. B. Yim, andE. R. Stadtman. 1990. Manganese (II) catalyzes the bicarbonate dependent oxidation of amino acids by hydrogen peroxide and the amino acid-facilitated dismutation of hydrogen peroxide.Proc. Natl. Acad. Sci. U.S.A. 87:389–395.

    Google Scholar 

  5. Yim, M. B., B. S. Berlett, P. B. Chock, andE. R. Stadtman. 1990. Manganese (II) bicarbonate-mediated catalytic activity for hydrogen peroxide dismutation and amino acid oxidation: Detection of free radical intermediates.Proc. Natl. Acad. Sci. U.S.A. 87:394–398.

    Google Scholar 

  6. Phan, S. H., D. E. Cannon, J. Varani, U. S. Ryan, andP. A. Ward. 1989. Xanthine oxidase activity in rat pulmonary artery endothelial cells and its alteration by activated neutrophils.Am. J. Pathol. 134:1201–1211.

    Google Scholar 

  7. Varani, J., S. H. Phan, D. F. Gibbs, U. S. Ryan, andP. A. Ward. 1990. H2O2-mediated cytotoxicity of rat pulmonary artery endothelial cells: Changes in ATP and purine products and effects of protective interventions.Lab. Invest. 63:683–689.

    Google Scholar 

  8. Varani, J., S. E. G. Fligiel, G. O. Till, R. G. Kunkel, U. S. Ryan, andP. A. Ward. 1895. Pulmonary endothelial cell killing by human neutrophils: Possible involvement of hydroxyl radical.Lab. Invest. 53:656–661.

    Google Scholar 

  9. Varani, J., M. J. Bendelow, D. E. Sealey, S. L. Kunkel, D. E. Gannon, U. S. Ryan, andP. A. Ward. 1988. Tumor necrosis factor enhances susceptibility of vascular endothelial cells to neutrophil-mediated killing.Lab. Invest. 59:292–296.

    Google Scholar 

  10. Johnson, K. J., andP. A. Ward. 1974. Acute immunologie alveolitis.J. Clin. Invest. 54:349–356.

    Google Scholar 

  11. Yamazaki, I., andL. H. Piette. 1990. ESR spin-trapping studies on the reaction of Fe2+ with H2O2-reactive species in oxygen toxicity in biology.J. Biol. Chem. 265:13589–13594.

    Google Scholar 

  12. Beckman, J. S., R. L. Minor, Jr., andB. A. Freeman. 1986. Augmentation of antioxidant enzymes in vascular endothelium.Free Radical Biol. Med. 2:359–363.

    Google Scholar 

  13. Beckman, J. S., R. L. Minor, Jr., C. W. White, J. E. Repine, G. M. Rosen, andB. A. Freeman. 1988. Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance.J. Biol. Chem. 263:6884–6890.

    Google Scholar 

  14. Freeman, B. A., S. L. Young, andJ. D. Cropo. 1983. Liposome-mediated augmentation of superoxide dismutase in endothelial cells prevents oxygen injury.J. Biol. Chem. 258:12534–12538.

    Google Scholar 

  15. Parenti, M., L. Rusconi, V. Cappabianca, E. A. Parati, andA. Groppetti. 1988. Role of dopamine in manganese neurotoxicity.Brain Res. 473:236–242.

    Google Scholar 

  16. Skreb, Y., andB. Nagy. 1984. Cell survival after the combined action of manganese (MnCl2) and X-rays in synchronized Chinese hamster cells.Arch. Toxlcol. 56:29–36.

    Google Scholar 

  17. Chandra, S. V., andG. S. Shukla, andR. C. Murthy. 1979. Effect of stress on the response of rat brain to manganese.Toxicol. Appl. Pharmacol. 47:603–608.

    Google Scholar 

  18. Halatcheva, L., andP. Kinolova. 1980. The effect of heavy metais (lead, manganese, mercury) on the concentration of free amino acids in the liver of rats.Arch. Toxicol. (Suppl) 4:355–359.

    Google Scholar 

  19. Webster, W. S., andA. A. Valois. 1987. Reproductive toxicology of manganese in rodents, including exposure during the postnatal period.Neurotoxicology 8:437–442.

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Michigan, Ann Arbor, Michigan

    James Varani, Douglas F. Gibbs, Partha S. Mukhopadhyay, Chris Sulavik, Kent J. Johnson & Peter A. Ward

  2. Department of Oral Biology, Hebrew University, Jerusalem, Israel

    Isaac Ginsburg

  3. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan

    Joel M. Weinberg

  4. Division of Health Sciences, Monsanto, Co., St. Louis, Missouri

    Una S. Ryan

Authors
  1. James Varani
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  2. Isaac Ginsburg
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  3. Douglas F. Gibbs
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  4. Partha S. Mukhopadhyay
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  5. Chris Sulavik
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  6. Kent J. Johnson
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  7. Joel M. Weinberg
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  8. Una S. Ryan
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  9. Peter A. Ward
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Varani, J., Ginsburg, I., Gibbs, D.F. et al. Hydrogen peroxide-induced cell and tissue injury: Protective effects of Mn2+ . Inflammation 15, 291–301 (1991). https://doi.org/10.1007/BF00917314

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