Inhibitory action of dipyrone on rat thyroid peroxidase and lactoperoxidase activities

Previous studies have shown that phenylbutazone, another pyrazolone, inhibits thyroid peroxidase activity and interferes with iodide organification. We have developed "in vitro" studies with rat particulated peroxidase and lactoperoxidase (LPO) to study the effects of dipyrone upon thyroid peroxidase and to determine the type of inhibition. The 3-monoiodothyrosine (MIT) and 3,5-diiodothyrosine (DIT) synthesis was markedly affected by 6 X 10(-4) M dipyrone with inhibitions of 59% and 30% respectively. No difference was observed with lower concentrations. Inhibition of peroxidase activity (Triiodide assay) was found when crude rat peroxidase preparations and LPO were incubated with dipyrone in concentrations ranging from 10(-3) M to 10(-8) M, with a Ki of 2.5 X 10(-5) M and 4 X 10(-5) M respectively. Guaiacol peroxidation was scarcely affected by the action of the drug; 10(-3) M produced inhibition of 50%. Line weaver-Burk: plots were used to investigate the inhibition of LPO activity by dipyrone. The inhibition by the drug was competitive with the iodide. We may conclude that dipyrone and other drugs of the pyrazolone group act upon peroxidase activity "in vitro", by an inhibition of competitive type and in presence of iodide.