Effect of dimethylthiourea on the neutrophil myeloperoxidase pathway

A. L. Sagone, R. M. Husney, M. D. Wewers, D. J. Herzyk, W. B. Davis

Research output: Contribution to journalArticle

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Abstract

The sulfur-centered compound dimethylthiourea (DMTU) affords antioxidant protection in animal models of acute lung injury, an effect that has been attributed to its OH· scavenging properties. Although DMTU can also react with H2O2 in certain experimental systems, the effect of DMTU on the neutrophil myeloperoxidase (MPO) pathway has not been studied. DMTU (1-10 mM) completely blocked stable oxidants and hypochlorous acid formation by phorbol myristate acetate- and zymosan-stimulated neutrophils. DMTU also provided complete inhibition when incubated with cell-free supernatants after the formation of the MPO products. DMTU prevented the oxidative inactivation of α1-antitrypsin by neutrophil-stable oxidants. Evidence that DMTU was oxidized by the MPO products was obtained by titration of oxidized DMTU with reduced glutathione. Surprisingly, supernatants from cells incubated with DMTU (10 mM) consumed two- to threefold higher amounts of reduced glutathione than supernatants from cells incubated with taurine (15 mM). Metabolic studies with stimulated neutrophils and experiments with the MPO enzyme system in a cell-free system suggested that DMTU acts by scavenging the products of the MPO pathway rather than by blocking H2O2 production in the intact cell. These findings demonstrate that DMTU blocks the neutrophil MPO pathway in addition to its known ability to scavenge other reactive O2 species. The capacity of DMTU to scavenge MPO products may explain some of its protective effects in acute lung injury.

Original languageEnglish (US)
Pages (from-to)1056-1062
Number of pages7
JournalJournal of Applied Physiology
Volume67
Issue number3
StatePublished - Jan 1 1989

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Peroxidase
Neutrophils
Acute Lung Injury
Oxidants
Glutathione
1,3-dimethylthiourea
Hypochlorous Acid
Sulfur Compounds
Zymosan
Cell-Free System
Taurine
Tetradecanoylphorbol Acetate
Animal Models
Antioxidants

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Sagone, A. L., Husney, R. M., Wewers, M. D., Herzyk, D. J., & Davis, W. B. (1989). Effect of dimethylthiourea on the neutrophil myeloperoxidase pathway. Journal of Applied Physiology, 67(3), 1056-1062.

Effect of dimethylthiourea on the neutrophil myeloperoxidase pathway. / Sagone, A. L.; Husney, R. M.; Wewers, M. D.; Herzyk, D. J.; Davis, W. B.

In: Journal of Applied Physiology, Vol. 67, No. 3, 01.01.1989, p. 1056-1062.

Research output: Contribution to journalArticle

Sagone, AL, Husney, RM, Wewers, MD, Herzyk, DJ & Davis, WB 1989, 'Effect of dimethylthiourea on the neutrophil myeloperoxidase pathway', Journal of Applied Physiology, vol. 67, no. 3, pp. 1056-1062.
Sagone AL, Husney RM, Wewers MD, Herzyk DJ, Davis WB. Effect of dimethylthiourea on the neutrophil myeloperoxidase pathway. Journal of Applied Physiology. 1989 Jan 1;67(3):1056-1062.
Sagone, A. L. ; Husney, R. M. ; Wewers, M. D. ; Herzyk, D. J. ; Davis, W. B. / Effect of dimethylthiourea on the neutrophil myeloperoxidase pathway. In: Journal of Applied Physiology. 1989 ; Vol. 67, No. 3. pp. 1056-1062.
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