[en] Numerous ototoxic drugs, such as some antibiotics and chemotherapeutics, are both cochleotoxic and vestibulotoxic (causing hearing loss and vestibular disorders). However, the impact of some industrial cochleotoxic compounds on the vestibular receptor, if any, remains unknown. As in vivo studies are long and expensive, there is considerable need for predictive and cost-effective in vitro models to test ototoxicity. Here, we present an organotypic model of cultured ampullae harvested from rat neonates. When cultured in a gelatinous matrix, ampulla explants form an enclosed compartment that progressively fills with a high-potassium (K+) endolymph-like fluid. Morphological analyses confirmed the presence of a number of cell types, sensory epithelium, secretory cells, and canalar cells. Treatments with inhibitors of potassium transporters demonstrated that the potassium homeostasis mechanisms were functional. To assess the potential of this model to reveal the toxic effects of chemicals, explants were exposed for either 2 or 72 h to styrene at a range of concentrations (0.5-1 mM). In the 2-h exposure condition, K+ concentration was significantly reduced, but ATP levels remained stable, and no histological damage was visible. After 72 h exposure, variations in K+ concentration were associated with histological damage and decreased ATP levels. This in vitro 3D neonatal rat ampulla model therefore represents a reliable and rapid means to assess the toxic properties of industrial compounds on this vestibular tissue, and can be used to investigate the specific underlying mechanisms.
Disciplines :
Otolaryngology
Author, co-author :
Tallandier, Valentin ; Université de Liège - ULiège > GIGA > GIGA Neurosciences ; French Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS), Toxicology and Biomonitoring Division, Vandoeuvre les Nancy, France, DevAH EA 3450 - Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité-Université de Lorraine, F-54500 Vandœuvre, France
Merlen, L; French Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS), Toxicology and Biomonitoring Division, Vandoeuvre les Nancy, France
Chalansonnet, M; French Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS), Toxicology and Biomonitoring Division, Vandoeuvre les Nancy, France. Electronic address: monique.chalansonnet@inrs.fr
Boucard, S; French Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS), Toxicology and Biomonitoring Division, Vandoeuvre les Nancy, France
Thomas, A; French Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS), Toxicology and Biomonitoring Division, Vandoeuvre les Nancy, France
Venet, T; French Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS), Toxicology and Biomonitoring Division, Vandoeuvre les Nancy, France, DevAH EA 3450 - Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité-Université de Lorraine, F-54500 Vandœuvre, France
Pouyatos, B; French Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS), Toxicology and Biomonitoring Division, Vandoeuvre les Nancy, France, DevAH EA 3450 - Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité-Université de Lorraine, F-54500 Vandœuvre, France
Language :
English
Title :
Three-dimensional cultured ampullae from rats as a screening tool for vestibulotoxicity: Proof of concept using styrene.
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