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.
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Abbreviations
- CV-ANOVA:
-
Cross-validation analysis of variance
- FT3:
-
Free triiodothyronine
- FT4:
-
Free thyroxine
- FWHM:
-
Full width at half maximum
- ITB:
-
Iodine thyroid blocking
- KI:
-
Potassium iodide
- LC/MS:
-
Liquid chromatography coupled with mass spectrometry
- m/z :
-
Mass-to-charge ratio
- NOAEL:
-
No-observed adverse effect limit
- PLS-DA:
-
Partial least squares–discriminant analysis
- PRIODAC:
-
Repeated stable iodide prophylaxis in accidental radioactive releases
- TSH:
-
Thyroid-stimulating hormone
- VIP:
-
Variable importance in projection
- WHO:
-
World Health Organization
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Acknowledgements
This study is a part of the PRIODAC research program supported by the French National Research Agency (ANR) and the Investing for the Future program (Grant #11-RSNR-0019, 2014). The authors thank the Pharmacie Centrale des Armées—French Armed Forces Central Pharmacy—for providing the KI solution and F. Voyer, A. Sache and R. Granger for animal care.
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CR performed the metabolomics analyses and contribute to data analyses and manuscript writing, DL contributed to study design and manuscript writing, SB performed analyses, PG and FC-M contributed to manuscript writing, MB and MS designed the study and contributed to manuscript writing, J-CM contributed to study design, data analyses and manuscript writing.
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Supplemental Fig. 1
Thyroid YWHAH or tyrosine hydroxylase or tyrosine 3-monoxygenase (A) and thyroid peroxidase (B) gene expression in the thyroid of male rats collected 30 days after completion of the ITB strategy using 1 mg/kg/day over 8 days. Microarray data (published in Lebsir, D., Cohen, D., Manens, L., Grison, S., Tack, K., Benderitter, M., Pech, A., Lestaevel, P., and Souidi, M. (2018). Toxicology of repeated iodine thyroid blocking in adult rat. Journal of Pharmaceutical Research3(1), 1–8). P value after t-test, n=5 rats per group (PDF 508 kb)
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Rosique, C., Lebsir, D., Benatia, S. et al. Metabolomics evaluation of repeated administration of potassium iodide on adult male rats. Arch Toxicol 94, 803–812 (2020). https://doi.org/10.1007/s00204-020-02666-w
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DOI: https://doi.org/10.1007/s00204-020-02666-w