Laboratório de Endocrinologia Experimental-LEEx, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil; Programa de Pós-graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
Laboratório de Endocrinologia Experimental-LEEx, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil; Programa de Pós-graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Brazil.
Mol Cell Endocrinol. 2022 Aug 1;553:111689. doi: 10.1016/j.mce.2022.111689. Epub 2022 Jun 8.
Tributyltin (TBT) is an endocrine disruptor used as a biocide in nautical paints. Even though many TBT effects in marine species are known, data in mammals are scarce, especially regarding the thyroid gland. The present study aimed to evaluate the effect of a subchronic exposure to TBT on thyroid oxidative stress of female Wistar rats. Rats received vehicle (control group), 200 or 1000 ng TBT/kg body weight/day for 40 days. After euthanasia, one part of the thyroids were collected in order to assess iodide uptake; activity and/or mRNA expression of thyroperoxidase (TPO) and dual oxidases (DUOXs); activity and/or mRNA expression of catalase, glutathione peroxidase, superoxide dismutase and NADPH oxidase 4 (CAT, GPx, SOD and NOX4); 4-hydroxynonenal (4-HNE) expression and total thiol groups levels; and mRNA expression of estrogen receptors alpha and beta (ERα and ERβ). The remaining part of the thyroid was processed for morphological analysis of estrogen receptor alpha (ERα) and for collagen deposition. Iodide uptake was not changed with treatments. TPO activity and expression were increased in the TBT1000 group (259.81% and 95.17%). The activity, but not mRNA, of CAT (17.36% TBT200; 27.10% TBT1000) and GPx (29.24% TBT200; 28.97% TBT1000) were decreased by TBT. SOD and NADPH oxidase activity, as well as thiol group and 4-HNE levels remained unchanged. Interstitial collagen deposition increased in the TBT200 group (39.54%). The mRNA expression of ERα increased in TBT-treated rats (44.87% TBT200; 36.43% TBT1000), while protein expression was increased but not reaching significance (TBT1000, p = 0.056) by TBT. Therefore, our results show that TBT increases TPO expression and reduces antioxidant enzyme activities in the thyroid gland leading to oxidative stress. Some of these effects could be mediated by the ERα pathway.
三丁基锡（TBT）是一种作为杀生物剂用于航海涂料的内分泌干扰物。尽管已经了解了许多海洋物种中的 TBT 效应，但哺乳动物的数据却很少，尤其是关于甲状腺的。本研究旨在评估亚慢性暴露于 TBT 对雌性 Wistar 大鼠甲状腺氧化应激的影响。大鼠接受载体（对照组），200 或 1000ng TBT/kg 体重/天，共 40 天。安乐死后，一部分甲状腺被收集以评估碘摄取；甲状腺过氧化物酶（TPO）和双氧化酶（DUOXs）的活性和/或 mRNA 表达；过氧化氢酶、谷胱甘肽过氧化物酶、超氧化物歧化酶和 NADPH 氧化酶 4（CAT、GPx、SOD 和 NOX4）的活性和/或 mRNA 表达；4-羟基壬烯醛（4-HNE）表达和总巯基水平；以及雌激素受体 alpha 和 beta（ERα 和 ERβ）的 mRNA 表达。甲状腺的其余部分用于雌激素受体 alpha（ERα）的形态分析和胶原蛋白沉积。碘摄取未随处理而改变。TPO 活性和表达在 TBT1000 组中增加（259.81%和 95.17%）。CAT（TBT200 组 17.36%；TBT1000 组 27.10%）和 GPx（TBT200 组 29.24%；TBT1000 组 28.97%）的活性而非 mRNA 减少。SOD 和 NADPH 氧化酶活性以及巯基和 4-HNE 水平保持不变。间质胶原蛋白沉积在 TBT200 组中增加（39.54%）。TBT 处理大鼠的 ERα mRNA 表达增加（TBT200 组 44.87%；TBT1000 组 36.43%），而 TBT 使 ERα 蛋白表达增加，但未达到显著水平（TBT1000，p=0.056）。因此，我们的结果表明，TBT 增加了甲状腺中的 TPO 表达并降低了抗氧化酶活性，导致氧化应激。其中一些影响可能是通过 ERα 途径介导的。
