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.