Isoniazid-mediated irreversible inhibition of the myeloperoxidase antimicrobial system of the human neutrophil and the effect of thyronines

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dc.contributor.authorVan Zyl J.M.
dc.contributor.authorBasson K.
dc.contributor.authorUebel R.A.
dc.contributor.authorVan der Walt B.J.
dc.date.accessioned2011-05-15T16:01:18Z
dc.date.available2011-05-15T16:01:18Z
dc.date.issued1989
dc.description.abstractDuring aerobic myeloperoxidase-catalysed oxidation of isoniazid at pH 7.8, compound III was generated. Oxidation of isoniazid or hydrazine sulphate at pH valu7es of 6.5 or 7.8 in a myeloperoxidase-H2O2 system caused considerable haem loss, which was associated with compound III formation. Haem loss and also compound III formation could be inhibited when 8 μM thyroxine was included in the reaction mixtures. During the reaction with isoniazid, an intense pink-coloured pigment with maximum absorbance at 500 nm was formed which could be bleached with ascorbate or hypochlorous acid. The pigment was more stable at pH 7.8 than at pH 6.5. A similar pink colour was generated when a mixture of isoniazid and thyroxine in alkaline solution was irradiated with light of wavelength > 300 nm. A possible product of thyroxine oxidation, 3,5-diiodotyrosine, could not protect the enzyme against isoniazid-mediated haem loss and no colour formation was observed. Haem loss was most extensive when isoniazid was oxidised in a myeloperoxidase system at pH 7.8 in the presence of 0.1 M NaCl. Thyroxine (8 μM), however, could still inhibit haem loss under these conditions. A good correlation was found between haem loss and irreversible loss of peroxidase activity.
dc.description.versionArticle
dc.identifier.citationBiochemical Pharmacology
dc.identifier.citation38
dc.identifier.citation14
dc.identifier.issn62952
dc.identifier.urihttp://hdl.handle.net/10019.1/11910
dc.subjectheme
dc.subjecthydrazine sulfate
dc.subjectisoniazid
dc.subjectmyeloperoxidase
dc.subjectthyroxine
dc.subjectantimicrobial activity
dc.subjecthuman
dc.subjecthuman cell
dc.subjectneutrophil
dc.subjectpriority journal
dc.subjectChlorides
dc.subjectHeme
dc.subjectHuman
dc.subjectHydrogen Peroxide
dc.subjectIsoniazid
dc.subjectModels, Chemical
dc.subjectNeutrophils
dc.subjectOxidation-Reduction
dc.subjectPeroxidase
dc.subjectSpectrophotometry, Ultraviolet
dc.subjectSupport, Non-U.S. Gov't
dc.subjectThyronines
dc.subjectThyroxine
dc.titleIsoniazid-mediated irreversible inhibition of the myeloperoxidase antimicrobial system of the human neutrophil and the effect of thyronines
dc.typeArticle
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