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. 1987 May 1;243(3):867–870. doi: 10.1042/bj2430867

The specificity of thiourea, dimethylthiourea and dimethyl sulphoxide as scavengers of hydroxyl radicals. Their protection of alpha 1-antiproteinase against inactivation by hypochlorous acid.

M Wasil 1, B Halliwell 1, M Grootveld 1, C P Moorhouse 1, D C Hutchison 1, H Baum 1
PMCID: PMC1147938  PMID: 2821995

Abstract

Thiourea and dimethylthiourea are powerful scavengers of hydroxyl radicals (.OH), and dimethylthiourea has been used to test the involvement of .OH in several animal models of human disease. It is shown that both thiourea and dimethylthiourea are scavengers of HOCl, a powerful oxidant produced by neutrophil myeloperoxidase. Hence the ability of dimethylthiourea to protect against neutrophil-mediated tissue damage cannot be used as evidence for a role of .OH in causing such damage. Dimethyl sulphoxide also reacts with HOCl, but at a rate that is probably too low to be biologically significant at dimethyl sulphoxide concentrations up to 10 mM. Neither mannitol nor desferrioxamine, at the concentrations normally used in radical-generating systems, appears to react with HOCl.

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Selected References

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  1. Albrich J. M., McCarthy C. A., Hurst J. K. Biological reactivity of hypochlorous acid: implications for microbicidal mechanisms of leukocyte myeloperoxidase. Proc Natl Acad Sci U S A. 1981 Jan;78(1):210–214. doi: 10.1073/pnas.78.1.210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cederbaum A. I., Dicker E., Rubin E., Cohen G. Effect of thiourea on microsomal oxidation of alcohols and associated microsomal functions. Biochemistry. 1979 Apr 3;18(7):1187–1191. doi: 10.1021/bi00574a011. [DOI] [PubMed] [Google Scholar]
  3. Dorogi P. L., Solomon A. K. Interaction of thiourea with band 3 in human red cell membranes. J Membr Biol. 1985;85(1):37–48. doi: 10.1007/BF01872004. [DOI] [PubMed] [Google Scholar]
  4. Fantone J. C., Ward P. A. Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol. 1982 Jun;107(3):395–418. [PMC free article] [PubMed] [Google Scholar]
  5. Fox R. B., Harada R. N., Tate R. M., Repine J. E. Prevention of thiourea-induced pulmonary edema by hydroxyl-radical scavengers. J Appl Physiol Respir Environ Exerc Physiol. 1983 Nov;55(5):1456–1459. doi: 10.1152/jappl.1983.55.5.1456. [DOI] [PubMed] [Google Scholar]
  6. Fox R. B. Prevention of granulocyte-mediated oxidant lung injury in rats by a hydroxyl radical scavenger, dimethylthiourea. J Clin Invest. 1984 Oct;74(4):1456–1464. doi: 10.1172/JCI111558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gillespie M. N., Kojima S., Kunitomo M., Jay M. Coronary and myocardial effects of activated neutrophils in perfused rabbit hearts. J Pharmacol Exp Ther. 1986 Dec;239(3):836–840. [PubMed] [Google Scholar]
  8. Green T. R., Fellman J. H., Eicher A. L. Myeloperoxidase oxidation of sulfur-centered and benzoic acid hydroxyl radical scavengers. FEBS Lett. 1985 Nov 11;192(1):33–36. doi: 10.1016/0014-5793(85)80037-5. [DOI] [PubMed] [Google Scholar]
  9. Grootveld M., Halliwell B. An aromatic hydroxylation assay for hydroxyl radicals utilizing high-performance liquid chromatography (HPLC). Use to investigate the effect of EDTA on the Fenton reaction. Free Radic Res Commun. 1986;1(4):243–250. doi: 10.3109/10715768609051634. [DOI] [PubMed] [Google Scholar]
  10. Grootveld M., Halliwell B. Aromatic hydroxylation as a potential measure of hydroxyl-radical formation in vivo. Identification of hydroxylated derivatives of salicylate in human body fluids. Biochem J. 1986 Jul 15;237(2):499–504. doi: 10.1042/bj2370499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Halliwell B., Gutteridge J. M. Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Arch Biochem Biophys. 1986 May 1;246(2):501–514. doi: 10.1016/0003-9861(86)90305-x. [DOI] [PubMed] [Google Scholar]
  12. Halliwell B., Gutteridge J. M. The importance of free radicals and catalytic metal ions in human diseases. Mol Aspects Med. 1985;8(2):89–193. doi: 10.1016/0098-2997(85)90001-9. [DOI] [PubMed] [Google Scholar]
  13. Halliwell B. Superoxide-dependent formation of hydroxyl radicals in the presence of iron chelates: is it a mechanism for hydroxyl radical production in biochemical systems? FEBS Lett. 1978 Aug 15;92(2):321–326. doi: 10.1016/0014-5793(78)80779-0. [DOI] [PubMed] [Google Scholar]
  14. Halliwell B. Use of desferrioxamine as a 'probe' for iron-dependent formation of hydroxyl radicals. Evidence for a direct reaction between desferal and the superoxide radical. Biochem Pharmacol. 1985 Jan 15;34(2):229–233. doi: 10.1016/0006-2952(85)90129-7. [DOI] [PubMed] [Google Scholar]
  15. Johnson K. J., Fantone J. C., 3rd, Kaplan J., Ward P. A. In vivo damage of rat lungs by oxygen metabolites. J Clin Invest. 1981 Apr;67(4):983–993. doi: 10.1172/JCI110149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kalyanaraman B., Sohnle P. G. Generation of free radical intermediates from foreign compounds by neutrophil-derived oxidants. J Clin Invest. 1985 May;75(5):1618–1622. doi: 10.1172/JCI111868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Moorhouse C. P., Halliwell B., Grootveld M., Gutteridge J. M. Cobalt(II) ion as a promoter of hydroxyl radical and possible 'crypto-hydroxyl' radical formation under physiological conditions. Differential effects of hydroxyl radical scavengers. Biochim Biophys Acta. 1985 Dec 13;843(3):261–268. doi: 10.1016/0304-4165(85)90147-3. [DOI] [PubMed] [Google Scholar]
  18. Tate R. M., Vanbenthuysen K. M., Shasby D. M., McMurtry I. F., Repine J. E. Oxygen-radical-mediated permeability edema and vasoconstriction in isolated perfused rabbit lungs. Am Rev Respir Dis. 1982 Nov;126(5):802–806. doi: 10.1164/arrd.1982.126.5.802. [DOI] [PubMed] [Google Scholar]
  19. Varani J., Fligiel S. E., Till G. O., Kunkel R. G., Ryan U. S., Ward P. A. Pulmonary endothelial cell killing by human neutrophils. Possible involvement of hydroxyl radical. Lab Invest. 1985 Dec;53(6):656–663. [PubMed] [Google Scholar]
  20. Ward P. A., Till G. O., Kunkel R., Beauchamp C. Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury. J Clin Invest. 1983 Sep;72(3):789–801. doi: 10.1172/JCI111050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wasil M., Halliwell B., Hutchison D. C., Baum H. The antioxidant action of human extracellular fluids. Effect of human serum and its protein components on the inactivation of alpha 1-antiproteinase by hypochlorous acid and by hydrogen peroxide. Biochem J. 1987 Apr 1;243(1):219–223. doi: 10.1042/bj2430219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weiss S. J. Oxygen, ischemia and inflammation. Acta Physiol Scand Suppl. 1986;548:9–37. [PubMed] [Google Scholar]
  23. Winterbourn C. C. Comparative reactivities of various biological compounds with myeloperoxidase-hydrogen peroxide-chloride, and similarity of the oxidant to hypochlorite. Biochim Biophys Acta. 1985 Jun 18;840(2):204–210. doi: 10.1016/0304-4165(85)90120-5. [DOI] [PubMed] [Google Scholar]
  24. Wong C., Fox R., Demling R. H. Effect of hydroxyl radical scavenging on endotoxin-induced lung injury. Surgery. 1985 Mar;97(3):300–307. [PubMed] [Google Scholar]

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