title: Oxidative stress in the thyroid gland: from harmlessness to hazard depending on the iodine content.
abstract: In basal conditions, thyroid epithelial cells produce moderate amounts of reactive oxygen species (ROS) that are physiologically required for thyroid hormone synthesis. They are not necessarily toxic because they are continuously detoxified either in the process of hormone synthesis or by endogenous antioxidant systems. Using a rat model of goiter formation and iodine-induced involution, we found that compared with control thyroids, the oxidative stress, assessed by the detection of 4-hydroxynonenal, was strongly enhanced both in hyperplastic and involuting glands. The level of antioxidant defenses (glutathione peroxidases and peroxiredoxins) was also up-regulated in both groups, although somewhat less in the latter. Of note, increased oxidative stress came along with an inflammatory reaction, but only in involuting glands, suggesting that although antioxidant systems can adequately buffer a heavy load of ROS in goiter, it is not necessarily the case in involuting glands. The effects of 15-deoxy-Delta(12,14)-prostaglandin J2 (15dPGJ2), an endogenous ligand of peroxisome proliferated-activated receptor gamma (PPARgamma) with antiinflammatory properties, were then investigated in involuting glands. This drug strongly reduced both 4-hydroxynonenal staining and the inflammatory reaction, indicating that it can block iodine-induced cytotoxicity. When experiments were carried out with the PPARgamma antagonist, bisphenol A diglycidyl ether, 15dPGJ2-induced effects remained unchanged, suggesting that these effects were not mediated by PPARgamma. In conclusion, thyroid epithelial cells are well adapted to endogenously produced ROS in basal and goitrous conditions. In iodine-induced goiter involution, the increased oxidative stress is accompanied by inflammation that can be blocked by 15dPGJ2 through PPARgamma-independent protective effects.
authors: Unité de Morphologie Expérimentale (MOEX), Université catholique de Louvain, UCL-5251, B-1200 Brussels, Belgium.
authors: Sylvie
authors: S
authors: Poncin
authors: Anne-Catherine
authors: AC
authors: Gérard
authors: Marie
authors: M
authors: Boucquey
authors: Maximin
authors: M
authors: Senou
authors: Pedro Buc
authors: PB
authors: Calderon
authors: Bernard
authors: B
authors: Knoops
authors: Benoît
authors: B
authors: Lengelé
authors: Marie-Christine
authors: MC
authors: Many
authors: Ides M
authors: IM
authors: Colin
mesh_terms: D000465:Algorithms; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001559:Benzhydryl Compounds; D002273:Carcinogens / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D018450:Disease Progression; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006042:Goiter / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D007455:Iodine / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D047495:PPAR gamma / Q000378:metabolism / Q000502:physiology; D054464:Peroxiredoxins / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012074:Remission Induction; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000502:physiology*; D013966:Thyroiditis / Q000139:chemically induced / Q000473:pathology; D000098826:Bisphenol A Compounds
chemical_list: D000975:Antioxidants; D001559:Benzhydryl Compounds; D002273:Carcinogens; D004852:Epoxy Compounds; D005979:Glutathione Peroxidase; D007455:Iodine; D047495:PPAR gamma; D054464:Peroxiredoxins; D015230:Prostaglandin D2; C477819:15-deoxyprostaglandin J2; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds