tailieunhanh - Báo cáo khoa học: Thyroid Ca2+/NADPH-dependent H2O2 generation is partially inhibited by propylthiouracil and methimazole

H2O2 generation is a limiting step in thyroid hormone bio-synthesis. Biochemical studies have confirmed that H2O2is generated by a thyroid Ca 2+ /NADPH-dependent oxidase. Decreased H2O2 availability may be another mechanism of inhibition of thyroperoxidase activity produced by thio-ureylene compounds, as propylthiouracil (PTU) and methimazole (MMI) are antioxidant agents. Therefore, we analyzed whether PTU or MMI could scavenge H2O2or inhibit thyroidNADPHoxidase activityin vitro. | Eur. J. Biochem. 270 2363-2368 2003 FEBS 2003 doi Thyroid Ca2 NADPH-dependent H2O2 generation is partially inhibited by propylthiouracil and methimazole Andrea C. Freitas Ferreira Luciene de Carvalho Cardoso Doris Rosenthal and Denise Pires de Carvalho Laboratorio de Fisiologia Endocrina Instituto de Biofisica Carlos Chagas Filho Universidade Federal do Rio de Janeiro Brazil H2O2 generation is a limiting step in thyroid hormone biosynthesis. Biochemical studies have confirmed that H2O2 is generated by a thyroid Ca2 NADPH-dependent oxidase. Decreased H2O2 availability may be another mechanism of inhibition of thyroperoxidase activity produced by thioureylene compounds as propylthiouracil PTU and methimazole MMI are antioxidant agents. Therefore we analyzed whether PTU or MMI could scavenge H2O2 or inhibit thyroid NADPH oxidase activity in vitro. Our results show that PTU and thiourea did not significantly scavenge H2O2. However MMI significantly scavenged H2O2 at high concentrations. Only MMI was able to decrease the amount of H2O2 generated by the glucose-glucose oxidase system. On the other hand both PTU and MMI were able to partially inhibit thyroid NADPH oxidase activity in PTU did not scavenge H2O2 under the conditions used here we presume that this drug may directly inhibit thyroid NADPH oxidase. Also at the concentration necessary to inhibit NADPH oxidase activity MMI did not scavenge H2O2 also suggesting a direct effect of MMI on thyroid NADPH oxidase. In conclusion this study shows that MMI but not PTU is able to scavenge H2O2 in the micromolar range and that both PTU and MMI can impair thyroid H2O2 generation in addition to their potent thyroperoxidase inhibitory effects. Keywords antithyroid drugs H2O2 NADPH oxidase thyroid. The mechanism by which antithyroid drugs such as propylthiouracil PTU and 1-methyl-2-mercaptoimidazole or methimazole MMI block thyroid hormone biosynthesis has been well studied 1 . Both are