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Am J Pathol ; 176(3): 1355-63, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20093493

RESUMO

Goiter is associated with increased oxidative stress (OS). We studied the effects of an anti-inflammatory agent, 15 deoxy-Delta12,14-prostaglandin J2 (15dPGJ2) and an antioxidant, N-acetylcysteine (NAC), on OS, thyroid function, and goiter expansion in a model of goiter induced by propylthiouracil (PTU) or perchlorate. OS was assessed by the immunodetection of 4-hydroxynonenal, thyroid function by measuring thyroxin (T4) and thyrotropin (TSH) plasma levels and detecting T4-rich thyroglobulin (Tg-I), and goiter expansion by weighing the thyroids and measuring cell proliferation (PCNA and cyclin D1 immunodetection). In both PTU and perchlorate-induced goiters, OS, TSH plasma levels, thyroid weight, and cell proliferation were strongly enhanced, whereas Tg-I expression was negative. All these parameters were reversed by NAC and 15dPGJ2 in PTU-goiters. In perchlorate-goiters, TSH plasma levels remained elevated and Tg-I-negative after NAC or 15dPGJ2 treatment. OS was reduced by NAC, but not by 15dPGJ2. In addition, NAC reduced PCNA and cyclin D1 immunostainings, as well as thyroid weight, whereas 15dPGJ2 influenced neither thyroid weight nor cell proliferation. In conclusion, NAC and 15dPGJ2 overcome PTU- but not perchlorate-induced effects. The retrieval of hormonal synthesis may result from direct chemical interactions between PTU and NAC/15dPGJ2. Although 15dPGJ2 has no effect in perchlorate-goiters, the reduction of OS by NAC is associated with altered goiter development, making OS a required condition for the growth of the thyroid gland.


Assuntos
Estresse Oxidativo , Glândula Tireoide/patologia , Acetilcisteína/farmacologia , Animais , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Feminino , Bócio/sangue , Bócio/patologia , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Percloratos , Peroxirredoxinas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Propiltiouracila , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacologia , Ratos , Ratos Wistar , Glândula Tireoide/efeitos dos fármacos , Tiroxina/sangue
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