title: Thyroid Ca2+/NADPH-dependent H2O2 generation is partially inhibited by propylthiouracil and methimazole.
abstract: 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 vitro. As 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.
authors.affiliation: Laboratório de Fisiologia Endócrina, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Andrea C Freitas
authors.initials: AC
authors.lastname: Ferreira
authors.forename: Luciene
authors.initials: L
authors.lastname: de Carvalho Cardoso
authors.forename: Doris
authors.initials: D
authors.lastname: Rosenthal
authors.forename: Denise Pires
authors.initials: DP
authors.lastname: de Carvalho
mesh_terms: D013956:Antithyroid Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology*; D009249:NADP / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011441:Propylthiouracil / Q000494:pharmacology*; D013961:Thyroid Gland / Q000378:metabolism*; D013997:Time Factors
chemical_list: D013956:Antithyroid Agents; D009249:NADP; D008713:Methimazole; D011441:Propylthiouracil; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D010100:Oxygen; D002118:Calcium