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代谢组学评价成年雄性大鼠重复给予碘化钾后的情况。

Metabolomics evaluation of repeated administration of potassium iodide on adult male rats.

机构信息

Aix Marseille Univ, INSERM, INRAE, C2VN, BioMeT, Marseille, France.

Institut de Radioprotection Et de Sûreté Nucléaire (IRSN), PSE-SANTE, 92260, Fontenay-aux-Roses, France.

出版信息

Arch Toxicol. 2020 Mar;94(3):803-812. doi: 10.1007/s00204-020-02666-w. Epub 2020 Feb 11.

Abstract

The long-lasting consequence of a new iodine thyroid blocking strategy (ITB) to be used in case of nuclear accident is evaluated in male Wistar rats using a metabolomics approach applied 30 days after ITB completion. The design used 1 mg/kg/day of KI over 8 days. Thyroid hormones remained unchanged, but there was a metabolic shift measured mainly in thyroid then in plasma and urine. In the thyroid, tyrosine metabolism associated to catecholamine metabolism was more clearly impacted than thyroid hormones pathway. It was accompanied by a peripheral metabolic shift including metabolic regulators, branched-chain amino acids, oxidant stress and inflammation-associated response. Our results suggested that iodide intake can impact gut microbiota metabolism, which was related to host metabolic regulations including in the thyroid. As there were no clear clinical signs of dysfunction or toxicity, we concluded that the measured metabolomics response to the new ITB strategy, especially in thyroid, is unlikely to reveal a pathological condition but a shift towards a new adaptive homeostatic state, called 'allostatic regulation'. The question now is whether or not the shift is permanent and if so at what cost for long-term health. We anticipate our data as a start point for further regulatory toxicity studies.

摘要

采用代谢组学方法,在碘甲状腺阻断策略(ITB)完成 30 天后,评估用于核事故的新碘甲状腺阻断策略(ITB)的长期后果。设计方案为每天使用 1mg/kg 的碘化钾(KI)持续 8 天。甲状腺激素保持不变,但代谢发生了变化,主要在甲状腺,然后在血浆和尿液中。在甲状腺中,与儿茶酚胺代谢相关的酪氨酸代谢比甲状腺激素途径受到更明显的影响。同时还伴随着外周代谢变化,包括代谢调节剂、支链氨基酸、氧化应激和炎症相关反应。我们的结果表明,碘的摄入会影响肠道微生物群的代谢,这与宿主的代谢调节有关,包括在甲状腺中。由于没有明显的功能障碍或毒性的临床迹象,我们得出结论,新 ITB 策略所测量的代谢组学反应,尤其是在甲状腺中,不太可能揭示病理状况,而是向新的适应性稳态(称为“全身调节”)转变。现在的问题是这种转变是否是永久性的,如果是,对长期健康的代价是什么。我们预计我们的数据将作为进一步的监管毒性研究的起点。

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