Styrene alters potassium endolymphatic concentration in a model of cultured utricle explants

• Published in: Toxicology in vitro Vol. 67; p. 104915
• Main Authors: Tallandier, V., Merlen, L., Boucard, S., Thomas, A., Venet, T., Chalansonnet, M., Gauchard, G., Campo, P., Pouyatos, B.
• Format: Journal Article Web Resource
• Language: English
• Published: England Elsevier Ltd 01.09.2020; Elsevier Science Ltd; Elsevier
• Subjects: Anatomie (cytologie, histologie, embryologie...) & physiologie; Anatomy (cytology, histology, embryology...) & physiology; Animals; Animals, Newborn; Balance; Cochlea; Cysts; Cytoplasm; Deregulation; Efflux; Endolymph; Endolymph - drug effects; Endolymph - metabolism; Epidemiology; Epithelial cells; Epithelium; Explants; Female; General Medicine; Hair cells; Homeostasis; Life Sciences; Microelectrodes; Neurotoxicity; Organotypic culture; Ototoxicity; Potassium; Potassium - metabolism; Rat; Rats, Long-Evans; Receptors; Saccule and Utricle; Saccule and Utricle - drug effects; Saccule and Utricle - metabolism; Saccule and Utricle - pathology; Sciences du vivant; Styrene; Styrene - toxicity; Styrenes; Three dimensional models; Toxicology; Utricle; Vacuoles; Vestibular epithelium; Vestibular explants; Vestibular system; PBS; Rat; Organotypic culture; Na/K-ATPase; DMEM-F12; K; OHC; TC; DIV; P; 3D; Endolymph; Styrene; NKCC1; HC; Vestibular explants; Potassium; MET; DC
• ISSN: 0887-2333; 1879-3177; 1879-3177
• DOI: 10.1016/j.tiv.2020.104915

Despite well-documented neurotoxic and ototoxic properties, styrene remains commonly used in industry. Its effects on the cochlea have been extensively studied in animals, and epidemiological and animal evidence indicates an impact on balance. However, its influence on the peripheral vestibular receptor has yet to be investigated. Here, we assessed the vestibulotoxicity of styrene using an in vitro model, consisting of three-dimensional cultured newborn rat utricles filled with a high‑potassium (K+) endolymph-like fluid, called “cysts”. K+ entry in the cyst (“influx”) and its exit (“efflux”) are controlled by secretory cells and hair cells, respectively. The vestibular epithelium's functionality is thus linked to K+ concentration, measured using a microelectrode. Known inhibitors of K+ efflux and influx validated the model. Cysts were subsequently exposed to styrene (0.25; 0.5; 0.75 and 1 mM) for 2 h or 72 h. The decrease in K+ concentration measured after both exposure durations was dose-dependent, and significant from 0.75 mM styrene. Vacuoles were visible in the cytoplasm of epithelial cells from 0.5 mM after 2 h and from 0.25 mM after 72 h. The results presented here are the first evidence that styrene may deregulate K+ homeostasis in the endolymphatic space, thereby altering the functionality of the vestibular receptor. •Styrene vestibulotoxicity was assessed in vitro with cultured rat utricles.•This model forms a sphere filled with high-K+ endolymph-like fluid.•Styrene causes a decrease of K+ concentration as soon as 2 h after treatment.•The decrease of K+ level was significant from 0.75 mM of styrene•Histopathological effects of styrene may appear prior to the decrease of K+ concentration.