1: Endocrinology. 2008 Jan;149(1):424-33. Epub 2007 Sep 20.

Oxidative stress in the thyroid gland: from harmlessness to hazard depending on
the iodine content.

Poncin S, Gérard AC, Boucquey M, Senou M, Calderon PB, Knoops B, Lengelé B, Many 
MC, Colin IM.

Unité de Morphologie Expérimentale (MOEX), Université catholique de Louvain,
UCL-5251, B-1200 Brussels, Belgium.

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.


PMID: 17884933 [PubMed - indexed for MEDLINE]

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