The influence of non-steroidal anti-inflammatory and antithyroid agents on myeloperoxidase-catalysed activities of human leucocytes.
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 H2O2-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 (DIT) 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 methylmercapto-imidazole (MMI) inhibited in vitro MPO-catalysed 131I delabelling of 131I-DIT at all concentrations between 10(-7) and 10(-2)M, whereas 131I-T4 delabelling was markedly stimulated at the same drug concentrations. On the other hand, 125I incorporation into 131I-DIT was not affected by increased concentrations of MMI up to 10(-5)M. At higher drug concentrations the drug caused inhibition of MPO-catalysed exchange of inorganic iodide for organic iodine in DIT.
D013956:Antithyroid Agents; D004105:Diiodotyrosine / Q000378:metabolism; D005439:Flufenamic Acid / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007962:Leukocytes / Q000201:enzymology / Q000378:metabolism*; D008954:Models, Biological; D009288:Naproxen / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D010587:Phagocytosis; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013010:Sonication; D013961:Thyroid Gland / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism
D013956:Antithyroid Agents; D007093:Imidazoles; D007457:Iodine Radioisotopes; D012710:Serum Albumin, Bovine; D009288:Naproxen; D005439:Flufenamic Acid; D004105:Diiodotyrosine; D010544:Peroxidases; D009195:Peroxidase; D013974:Thyroxine; D007213:Indomethacin