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首页> 外文期刊>The Journal of toxicological sciences >A new parameter that supports speculation on the possible mechanism of hypothyroidism induced by chemical substances in repeated-dose toxicity studies
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A new parameter that supports speculation on the possible mechanism of hypothyroidism induced by chemical substances in repeated-dose toxicity studies

机译：一个新的参数，支持推测重复剂量毒性研究中化学物质引起的甲状腺功能减退的可能机制

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Hypothyroidism induced by xenobiotic treatment was analyzed for possible underlying mechanism(s) on the basis of different responses of the thyroid gland and the liver, using a newly-created database of repeated-dose toxicity of 500 chemicals. Two mechanisms are proposed: direct inhibition of thyroid hormone biosynthesis in the thyroid gland, and stimulated degradation of thyroid hormone by induction of hepatic drug-metabolizing enzymes. In the database there were 10 chemicals inducing hypertrophy/hyperplasia of follicular cells in the thyroid gland and having data on thyroid glands. On the basis of the chemical structure and information available in the literature, we judged three chemicals to be typical thioamide derivatives that act directly on the thyroid gland, and the others as non-thioamide derivatives that were unlikely to have any direct action on the thyroid gland. All these chemicals were classified into two groups using the ratios of relative weight increase rate of thyroid gland versus that of the liver. These values were at least 1.7, but 3.2 or more in the most of the cases for thioamide derivatives, and 1.2 or less for non-thioamide derivatives. This background analysis suggests the feasibility of parameter-supported speculation on the possible underlying mechanism when new repeated-dose toxicity data on hypothyroidism becomes available.
机译：使用新创建的500种化学药品的重复剂量毒性数据库，根据甲状腺和肝脏的不同反应，分析了异种生物治疗引起的甲状腺功能减退症的可能的潜在机制。提出了两种机制：直接抑制甲状腺中甲状腺激素的生物合成，以及通过诱导肝脏药物代谢酶刺激甲状腺激素的降解。在数据库中，有10种化学物质可诱导甲状腺的滤泡细胞肥大/增生，并具有甲状腺的数据。根据文献中的化学结构和信息，我们认为三种化学物质是直接作用于甲状腺的典型硫代酰胺衍生物，而其他化学物质则是不太可能对甲状腺产生直接作用的非硫代酰胺衍生物。腺。根据甲状腺相对肝脏的相对体重增加率的比率，将所有这些化学物质分为两组。对于硫酰胺衍生物，这些值至少为1.7，但在大多数情况下为3.2或更高，对于非硫酰胺衍生物，这些值为1.2或更低。这项背景分析表明，当可获得有关甲状腺功能减退症的新的重复剂量毒性数据时，对可能的潜在机制进行参数支持的推测是可行的。

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