PLoS One. 2013 Sep 4;8(9):e73908. doi: 10.1371/journal.pone.0073908. eCollection 2013.
Thyroid iodide uptake through the sodium-iodide symporter (NIS) is not only an essential step for thyroid hormones biosynthesis, but also fundamental for the diagnosis and treatment of different thyroid diseases. However, part of patients with thyroid cancer is refractory to radioiodine therapy, due to reduced ability to uptake iodide, which greatly reduces the chances of survival. Therefore, compounds able to increase thyroid iodide uptake are of great interest. It has been shown that some flavonoids are able to increase iodide uptake and NIS expression in vitro, however, data in vivo are lacking. Flavonoids are polyhydroxyphenolic compounds, found in vegetables present in human diet, and have been shown not only to modulate NIS, but also thyroperoxidase (TPO), the key enzyme in thyroid hormones biosynthesis, besides having antiproliferative effect in thyroid cancer cell lines. Therefore, we aimed to evaluate the effect of some flavonoids on thyroid iodide uptake in Wistar rats in vivo. Among the flavonoids tested, rutin was the only one able to increase thyroid iodide uptake, so we decided to evaluate the effect of this flavonoid on some aspects of thyroid hormones synthesis and metabolism. Rutin led to a slight reduction of serum T4 and T3 without changes in serum thyrotropin (TSH), and significantly increased hypothalamic, pituitary and brown adipose tissue type 2 deiodinase and decreased liver type 1 deiodinase activities. Moreover, rutin treatment increased thyroid iodide uptake probably due to the increment of NIS expression, which might be secondary to increased response to TSH, since TSH receptor expression was increased. Thus, rutin might be useful as an adjuvant in radioiodine therapy, since this flavonoid increased thyroid iodide uptake without greatly affecting thyroid function.
甲状腺通过钠碘同向转运体(NIS)摄取碘不仅是甲状腺激素合成的必要步骤,也是诊断和治疗不同甲状腺疾病的基础。然而,部分甲状腺癌患者对放射性碘治疗有抗性,这是由于其摄取碘的能力降低,这大大降低了生存的机会。因此,能够增加甲状腺碘摄取的化合物具有很大的兴趣。已经表明,一些类黄酮能够增加体外碘摄取和 NIS 表达,然而,体内数据却缺乏。类黄酮是多羟基酚类化合物,存在于人类饮食中的蔬菜中,不仅能够调节 NIS,还能够调节甲状腺激素生物合成的关键酶——甲状腺过氧化物酶(TPO),此外,在甲状腺癌细胞系中还具有抗增殖作用。因此,我们旨在评估一些类黄酮在体内对 Wistar 大鼠甲状腺碘摄取的影响。在测试的类黄酮中,芦丁是唯一能够增加甲状腺碘摄取的类黄酮,因此我们决定评估这种类黄酮对甲状腺激素合成和代谢某些方面的影响。芦丁导致血清 T4 和 T3 略有减少,而血清促甲状腺激素(TSH)没有变化,并且显著增加下丘脑、垂体和棕色脂肪组织类型 2 脱碘酶的活性,降低肝脏类型 1 脱碘酶的活性。此外,芦丁治疗增加了甲状腺碘摄取,可能是由于 NIS 表达的增加,这可能是对 TSH 反应增加的结果,因为 TSH 受体的表达增加了。因此,芦丁可能作为放射性碘治疗的辅助剂有用,因为这种类黄酮增加了甲状腺碘摄取,而不会大大影响甲状腺功能。