Inhibitory effects of non-steroidal anti-inflammatory drugs on human myeloperoxidase

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Health & Medical Publishing Group
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.
CITATION: Theron, C. N., Lubbe, S. & Van Zyl, A. 1979. Inhibitory effects of non-steroidal anti-inflammatory drugs on human myeloperoxidase. South African Medical Journal, 56:670-675.
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Anti-inflammatory agents