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Pharmacy World and Science

, Volume 17, Issue 3, pp 76–80 | Cite as

Scavenging of reactive oxygen species by letosteine, a molecule with two blocked -SH groups

Comparison with free -SH drugs
  • B. Gressier
  • N. Lebegue
  • C. Brunet
  • M. Luyckx
  • T. Dine
  • M. Cazin
  • J. C. Cazin
Articles

Abstract

Acute production of reactive oxygen species by polymorphonuclear neutrophils during the respiratory burst may induce tissue injuries. In thisin vitro study, it was demonstrated that letosteine, a mucolytic agent containing two blocked thiol groups, had antioxidant activity, but only when it was first submitted to alkaline hydrolysis. In a cell-free system, hydrogen peroxide, hypochlorous acid and hydroxyl radical concentrations were reduced by half by letosteine concentrations of 200, 15 and 350 μol/l, respectively. The mechanism of letosteine action may be related to the -SH group liberatedin vitro by hydrolysis, which seemed to react by scavenging the reactive oxygen species in the same way as acetylcysteine and MESNA, freethiol drugs known for their antioxidant properties. So, letosteine, a compound with blocked -SH groups whichin vivo can metabolically become free, may have a therapeutic application in preventing oxidative tissue injury damage induced by the respiratory burst.

Keywords

Acetylcysteine Antioxidants Free radicals Hydrolysis Letosteine Mercaptoethanesulfonate Peroxides Sulfhydryl compounds Superoxide 

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References

  1. 1.
    Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1987;320:365–76.Google Scholar
  2. 2.
    Blake DR, Allen RE, Lunec J. Free radicals in biological system — a review orientated to inflammatory processes. Br Med Bull 1987;43(2):371–85.Google Scholar
  3. 3.
    Graf E, Mahoney JR, Bryant RG, Eaton JW. Iron-catalysed hydroxyl radical formation. J Biol Chem 1984;259(6):3620–4.Google Scholar
  4. 4.
    Wallaert B, Gressier B, Marquette CH, Gosset P, Remy-Jardin M, Mizon J,et al. Inactivation of alpha-1 proteinase inhibitor by alveolar inflammatory cells from smoking patients with or without emphysema. Am Rev Respir Dis 1993;147:1537–43.Google Scholar
  5. 5.
    Blaive B, Lapalus P, Lemoigne F. Etude clinique comparée de deux fluidifiants bronchiques: la S-carboxy-methyl-cystéine et la létostéine. Sem Hôp Paris 1978;54(29–32):983–6.Google Scholar
  6. 6.
    Gressier B, Cabanis A, Lebegue S, Brunet C, Dine T, Luyckx M,et al. Comparison of effectin vitro of two thiol containing drugs on human neutrophils hydrogen peroxide production. Methods Find Exp Clin Pharmacol 1993;15(2):101–5.Google Scholar
  7. 7.
    Gressier B, Cabanis A, Lebegue S, Brunet C, Dine T, Luyckx M,et al. Decrease of hypochlorous acid and hydroxyl radical generated by stimulated human neutrophils: comparisonin vitro of some thiol-containing drugs. Methods Find Exp Clin Pharmacol 1994;16(1):9–13.Google Scholar
  8. 8.
    Gazzani G, Fregnan GB, Vandoni G.In vitro protection by erdosteine against oxidative inactivation of alpha-1-antitrypsin by cigarette smoke. Respiration 1989;55:113–8.Google Scholar
  9. 9.
    Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action ofN-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, Superoxide anion and hypochlorous acid. Free Rad Biol Med 1989;6:593–7.Google Scholar
  10. 10.
    Pick E, Keisari Y. A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. J Immunol Methods 1980;38:161–70.Google Scholar
  11. 11.
    Weiss SJ, Klein R, Slivka A, Wei M. Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation. J Clin Invest 1982;70:598–607.Google Scholar
  12. 12.
    Halliwell B, Gutteridge JMC, Aruoma OI. The deoxyribose method: a simple ‘test tube’ assay for determination of rate constants for reactions of hydroxyl radical. Anal Biochem 1987;165:215–9.Google Scholar
  13. 13.
    Ramart-Lucas P. Spectres dans l'ultraviolet et spectres dans le visible. In: Traité de Chimie Organique. Vol. 2(1). 2nd edition. Paris: Masson et Cie, 1948:59–142.Google Scholar
  14. 14.
    Boniface M, Cazin JC, Cazin M, Luyckx J. Calcul sur ordinateur de la dose efficace par la méthode des probits. Application au calcul d'une dose léthale 50. Bull Soc Pharm Lille 1972;4:187–95.Google Scholar
  15. 15.
    Heffner JE, Repine JE. Pulmonary strategies of antioxidant defence. Am Rev Respir Dis 1989;140:531–54.Google Scholar
  16. 16.
    Reilly PM, Schiller HJ, Bulkley GB. Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am J Surg 1991;161:489–501.Google Scholar
  17. 17.
    Werns SW, Lucchesi BR. Inflammation and myocardial infarction. Cardiovasc Drugs Ther 1989;2(6):761–9.Google Scholar
  18. 18.
    Mundi H, Bjorksten B, Svanborg C, Ohman L, Dahlgren C. Extracellular release of reactive oxygen species from human neutrophils upon interaction withEscherichia coli strains causing renal scarring. Infect Immun 1991;59:4168–72.Google Scholar
  19. 19.
    Gey KF. Lipids, lipoproteins and antioxidants in cardiovascular dysfunction. Biochem Soc Trans 1990;18:1041–5.Google Scholar
  20. 20.
    Cochrane CG. Cellular injury by oxidants. Am J Med 1991; 91 Suppl 3C:23–30.Google Scholar
  21. 21.
    Hoidal JR, Niewoehner DE. Pathogenesis of emphysema. Chest 1983;83(4):679–85.Google Scholar
  22. 22.
    Repine JE. Scientific perspectives on adult respiratory distress syndrome. Lancet 1992;339:466–72.Google Scholar
  23. 23.
    Doelman CJA, Bast A. Oxygen radicals in lung pathology. Free Radic Biol Med 1990;9:381–400.Google Scholar
  24. 24.
    Borok Z, Buhl R, Grimes GJ, Bokser AD, Hubbard RC, Holroyd KJ,et al. Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis. Lancet 1991;338:215–6.Google Scholar
  25. 25.
    Gressier B, Lebegue S, Brunet C, Dine T, Luyckx M, Cazin M,et al. The effect of mesna in reversingin vitro the protease-antiprotease imbalance: its reaction on the MPO-H2O2 system and on human leukocyte elastase. Int J Pharm 1994;105:89–93.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1995

Authors and Affiliations

  • B. Gressier
    • 1
  • N. Lebegue
    • 1
  • C. Brunet
    • 1
  • M. Luyckx
    • 1
  • T. Dine
    • 1
  • M. Cazin
    • 1
  • J. C. Cazin
    • 1
  1. 1.Faculté de PharmacieLaboratoire de Pharmacologie, Pharmacocinétique et Pharmacie CliniqueLille CédexFrance

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