Inhibitory effects of non-steroidal anti-inflammatory drugs on human myeloperoxidase.
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 125I-thyroxine. Non-steroidal anti-inflammatory drugs (naproxen, indomethacin and flufenamic acid) showed a significant inhibitory effect on myeloperoxidase-catalysed iodination at concentrations of 10(-4)M 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(-3)M and 10(-7)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(-2)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 oxidizable 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.
D005439:Flufenamic Acid / Q000494:pharmacology*; D006139:Guaiacol / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007455:Iodine / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology; D009288:Naproxen / Q000494:pharmacology*; D009195:Peroxidase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D010544:Peroxidases / Q000037:antagonists & inhibitors*; D012710:Serum Albumin, Bovine / Q000378:metabolism
D012710:Serum Albumin, Bovine; D009288:Naproxen; D005439:Flufenamic Acid; D006139:Guaiacol; D007455:Iodine; D010544:Peroxidases; D009195:Peroxidase; D007213:Indomethacin