Browsing by Author "Lubbe, S."

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    The influence of non-steroidal anti-inflammatory and antithyroid agents on myeloperoxidase-catalysed activities of human leucocytes
    (Health & Medical Publishing Group, 1979) Van, Zyl A.; Lubbe, S.; Potgieter, A.; Van Zyl, J.
    Viable leucocytes obtained fresh from normal human subjects were shown to be able to catalyse the in vitro iodination of bovine serum albumin (BSA) in a H20 2-generating system. The rate and degree of iodination were greatly improved by sonication of the cells. A balanced salt solution was a more favourable medium than phosphate buffer for the myeloperoxidase (MPO)-catalysed iodination of whole cells and sonicated cells. Reactions known to be catalysed by other peroxidases (e.g_ thyroid peroxidase (TPO) and lactoperoxidase), such as inorganic iodide exchange for organic iodine in di-iodotyrosine (01T) and the de-iodination of thyroxine (T4)' were also catalysed by the sonicated leucocyte suspension in the system used. The non-steroidal anti-inflammatory drugs indomethacin, flufenamic acid and naproxen were far less effective inhibitors of MPO-catalysed BSA iodination of sonicated leucocytes at concentrations expected in blood with therapeutic dose levels than was observed earlier with TPO-catalysed in vitro iodination of BSA. The antithyroid drug ethylmercapto-imidazole (MM!) inhibited in vitro MPO-catalysed "'I delabelling of '''1·01l at all concentrations between 10·' and 10·'M, whereas "'I-T4 delabelling was markedly stimulated at the same drug concentrations. On the other hand, '251 incorporation into '''I-OIT was not affected by increased concentrations of MMI up to 10·'M. At higher drug concentrations the drug caused inhibition of MPO-catalysed exchange of inorganic iodide for organic iodine in Oil.
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    Inhibitory effects of non-steroidal anti-inflammatory drugs on human myeloperoxidase
    (Health & Medical Publishing Group, 1979) Theron, C. N.; Lubbe, S.; Van Zyl, A.
    Myeloperoxidase with an A420!280 ratio of 0,48 was prepared from normal human leucocytes. This partially purified preparation catalysed guaiacol oxidation, iodination of bovine serum albumin and de-iodination of 1251-thyroxine. Non-steroidal anti-inflammatory drugs (naproxen, indomethacin and f1ufenamic acid) showed a significant inhibitory effect on myeloperoxidase-catalysed iodination at concentrations of 10"4M and higher. Guaiacol also inhibited myeloperoxidase-catalysed iodination, and its iodination inhibition curve was nearly identical to that obtained with the anti-inflammatory drugs. At concentrations between 10"'M and 10"M the antiinflammatory drugs had very little or no effect on thyroxine de-iodination. Flufenamic acid and indomethacin, however, inhibited de-iodination significantly at a concentration of 10'M. It is postulated that non-steroidal anti-inflammatory drugs may inhibit myeloperoxidase-catalysed protein iodination by acting as oxidizable cofactors which compete with other oxidiza'ble substrates for oxidants formed by the peroxidase-hydrogen peroxide complex. In view of this and because the myeloperoxidase-hydrogen peroxide system may be involved in inflammatory tissue damage, the possibility should be considered that the action of non-steroidal anti-inflammatory drugs is at least partly attributable to a radical scavenging effect or to sequestration of oxidants.