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Evaluation de la vestibulotoxicité du styrène sur des explants d’utricules en culture

Publication scientifique

Styrene is still heavily used in industry despite its well-documented neurotoxic and ototoxic properties. While its effects on the cochlea following exposures have been extensively studied in animals, no study has shown the impact of this industrial compound on the peripheral vestibular receptor. However, several epidemiological studies and animal experiments have demonstrated deleterious effects of styrene on balance. The aim of this study is to evaluate the vestibulotoxicity of styrene by using “cysts”, i.e. inflated spheres filled with a high-potassium (K+) endolymph-like fluid, obtained from newborn rat utricles cultured in three-dimensional medium. In this in vitro model, K+ homeostasis is linked to the functionality of secretory cells and hair cells, respectively involved in K+ influx and efflux. Potassium concentration, measured using a K+-sensitive microelectrode, can therefore be used as a functional biomarker of the vestibular epithelium.
The model was first validated with gentamicin and gadolinium known to inhibit the influx of K+ blocking of hair cell’s stretch-activated channels. Both agents significantly increased K+ concentration, whereas targeting K+ secretion with ouabain and bumetanide – Na/K-ATPase and NKCC1 inhibitors – reduced K+ concentration. Cysts were then exposed to different concentrations of styrene (0.25; 0.5; 0.75 and 1 mM) either for 2h or 72 h. A dose-dependent K+ decrease in concentration was measured after 2-h and 72-h exposures. The decrease became significant from 0.75 mM for the short and long-duration exposures. Vacuoles could be seen in the cytoplasm of epithelial cells from 0.5 mM after 2-h and from 0.25 mM after 72- h exposure.
The results of the current study show for the first time that styrene may deregulate the K+ concentration in the endolymphatic space and thereby alter the functionality of the vestibular receptor.

Disciplines de recherche
Toxicologie expérimentale
Etudes Publications Communications