Fipronil-induced disruption of thyroid function in rats is mediated by increased total and free thyroxine clearances concomitantly to increased activity of hepatic enzymes - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Toxicology Année : 2009

Fipronil-induced disruption of thyroid function in rats is mediated by increased total and free thyroxine clearances concomitantly to increased activity of hepatic enzymes

Résumé

Fipronil is a widely used phytosanitary product and insecticide for pets. In the rat, fipronil can disrupt thyroid function by decreasing plasma concentrations of total thyroxine (T4) likely through increased T4 clearance. However, the mechanism of fipronil action on thyroid function remains unclear. The goals of the present study were to evaluate the effects of fipronil on thyroid hormone (TH) concentrations and elimination in the rat under well characterized plasma exposure to fipronil and its main metabolite fipronil sulfone. In thyroid-intact female rats, fipronil treatment (3 mg/(kg day) per os for 14 days) decreased both total and free TH plasma concentrations concomitantly to increased thyroid stimulating hormone plasma concentrations. A T4-free euthyroid-like model consisting of thyroidectomized rats treated with tri-iodothyronine (12 g/(kg day), sc)was developed to evaluate both total and free T4 clearances. In this model, fipronil treatment induced a twofold increase in total and free T4 clearances. The same fipronil treatment increased antipyrine clearance in thyroid-intact rats suggesting an increase in the activity of cytochrome P450 enzymes. Finally, this treatment was also associated with an increase in hepatic microsomal 4-nitrophenol UDP-glucuronosyltransferase activity involved in T4 glucuronidation. Thus, fipronil-induced thyroid disruption results from an increased rate of T4 elimination likely mediated by increased hepatic enzyme activity. Plasma concentrations of fipronil sulfone were at least 20-fold higher than those of fipronil. This highlights the need to further investigate the contribution of fipronil sulfone to the fipronil-induced thyroid disruption.
Fichier principal
Vignette du fichier
2009_Toxicology_Leghait_1.pdf (181.13 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02666328 , version 1 (31-05-2020)

Identifiants

Citer

Julien Leghait, Véronique V. Gayrard-Troy, Nicole Picard-Hagen, Marion Camp, Elisabeth Perdu, et al.. Fipronil-induced disruption of thyroid function in rats is mediated by increased total and free thyroxine clearances concomitantly to increased activity of hepatic enzymes. Toxicology, 2009, 255 (1-2), pp.38-44. ⟨10.1016/j.tox.2008.09.026⟩. ⟨hal-02666328⟩
33 Consultations
233 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More