Coelho-Palermo Cunha G, van Ravenzwaay B
BASF Aktiengesellschaft, Experimental Toxicology and Ecology, Z 470 D-67056 Ludwigshafen, Germany.
Regul Toxicol Pharmacol. 2007 Aug;48(3):270-8. doi: 10.1016/j.yrtph.2007.04.007. Epub 2007 May 10.
The perchlorate discharge assay (PDA) is potentially of high diagnostic value to distinguish between direct and indirect thyroid toxicity mechanisms, provided that standard treatment times are established and positive controls yield reproducible results. Therefore the PDA was evaluated after 2 and/or 4 weeks of treatment with positive control compounds in rats. Phenobarbital, Aroclor 1254 and beta-naphthoflavone (indirect toxic mechanism) enhanced thyroidal radioiodide accumulation, and the administration of potassium perchlorate had no effect on thyroid: blood (125)I ratio. Phenobarbital caused follicular cell hypertrophy and hyperplasia in the thyroid and centrilobular hypertrophy in the liver, without effects on serum triiodotyronine (T(3)), thyroxine (T(4)) levels. Thyroid-stimulating hormone (TSH) levels were moderately increased. Propylthiouracil (direct toxic mechanism) caused severe thyroid follicular cell hypertrophy and hyperplasia, reduced serum T(3) and T(4) levels and increased serum TSH levels, and reduced thyroidal radioiodide accumulation; perchlorate administration significantly reduced thyroid: blood (125)I ratio, demonstrating an iodide organification block. Potassium iodide (direct toxic mechanism) virtually blocked thyroidal radioiodide accumulation, without significant effects on serum T(3), T(4), and TSH levels and a microscopic correlate for higher thyroid weights. Thus, positive controls yielded reproducible results and we conclude that both the 2- and 4-week PDA is suitable to distinguish between direct and indirect thyroid toxicity mechanisms.
高氯酸盐排出试验（PDA）在区分直接和间接甲状腺毒性机制方面可能具有很高的诊断价值，前提是要确定标准治疗时间且阳性对照能产生可重复的结果。因此，在用阳性对照化合物对大鼠进行2周和/或4周治疗后，对PDA进行了评估。苯巴比妥、多氯联苯混合物Aroclor 1254和β-萘黄酮（间接毒性机制）可增强甲状腺对放射性碘的摄取，而给予高氯酸钾对甲状腺：血液（125）I比值没有影响。苯巴比妥导致甲状腺滤泡细胞肥大和增生以及肝脏小叶中心肥大，对血清三碘甲状腺原氨酸（T（3））、甲状腺素（T（4））水平没有影响。促甲状腺激素（TSH）水平适度升高。丙硫氧嘧啶（直接毒性机制）导致严重的甲状腺滤泡细胞肥大和增生，降低血清T（3）和T（4）水平并升高血清TSH水平，同时减少甲状腺对放射性碘的摄取；给予高氯酸盐可显著降低甲状腺：血液（125）I比值，表明存在碘有机化障碍。碘化钾（直接毒性机制）几乎完全阻断甲状腺对放射性碘的摄取，对血清T（3）、T（4）和TSH水平没有显著影响，且在显微镜下与甲状腺重量增加相关。因此，阳性对照产生了可重复的结果，我们得出结论，2周和4周的PDA均适用于区分直接和间接甲状腺毒性机制。
