Methimazole increases H2O2 toxicity in human thyroid epithelial cells.
Hydrogen peroxide (H(2)O(2)) is necessary for thyroid hormone production and also for intracellular signalling purposes. Owing to its oxidative properties, however, it is harmful to cells, and deregulation of thyroid oxidative state has been implicated in the pathology of thyroid cancer. In this project, we studied the effects of H(2)O(2) on morphology and histochemical indicators of differentiated function (intracellular thyroglobulin), ability to generate NADPH (glucose-6-phosphate dehydrogenase (G6PD) activity) and vitality (apoptosis assay) in human thyroid epithelial cells. We further evaluated whether methimazole, an antithyroid drug reported to have antioxidative properties, could counteract the effects of H(2)O(2). Our data demonstrate tolerance to H(2)O(2) in concentrations less than 0.3mM and harmful effects at higher concentrations. 10mM methimazole sensitizes the cells towards H(2)O(2), possibly due to a dose-dependent inhibition of G6PD. Our data demonstrate the importance of this antioxidative system and point towards a relevant, but seldom recognized, influence of methimazole.
Landex
N L
NL
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen N, Denmark. N.L.Landex@mai.ku.dk
Thomsen
J
J
Kayser
L
L
D013956:Antithyroid Agents / Q000819:agonists / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells / Q000201:enzymology* / Q000473:pathology; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity*; D008713:Methimazole / Q000819:agonists / Q000633:toxicity*; D016877:Oxidants / Q000819:agonists / Q000378:metabolism / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D013961:Thyroid Gland / Q000201:enzymology* / Q000473:pathology; D013963:Thyroid Hormones / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000201:enzymology
D013956:Antithyroid Agents; D016877:Oxidants; D013963:Thyroid Hormones; D008713:Methimazole; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase