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

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.

Author information

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.

Correspondence to Jean-Charles Martin.

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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 (2020). https://doi.org/10.1007/s00204-020-02666-w

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Keywords

  • Potassium iodide
  • Repeated iodine thyroid blocking
  • Thyroid gland
  • Metabolomics