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Neurotoxicity of Trimethyltin in Rat Cochlear Organotypic Cultures

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Abstract

Trimethyltin (TMT), which has a variety of applications in industry and agricultural, is a neurotoxin that is known to affect the auditory system as well as central nervous system of humans and experimental animals. However, the mechanisms underlying TMT-induced auditory dysfunction are poorly understood. To gain insights into the neurotoxic effect of TMT on the peripheral auditory system, we treated cochlear organotypic cultures with concentrations of TMT ranging from 5 to 100 μM for 24 h. Interestingly, TMT preferentially damaged auditory nerve fibers and spiral ganglion neurons in a dose-dependent manner, but had no noticeable effects on the sensory hair cells at the doses employed. TMT-induced damage to auditory neurons was associated with significant soma shrinkage, nuclear condensation, and activation of caspase-3, biomarkers indicative of apoptotic cell death. Our findings show that TMT is exclusively neurotoxicity in rat cochlear organotypic culture and that TMT-induced auditory neuron death occurs through a caspase-mediated apoptotic pathway.

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Acknowledgments

This research was supported in part by grant from the National Institute for Occupational Safety and Health, R01 OH010235, the National Nature Science Foundation of China (No. 81170912), the Major State Basic Research Development Program of China (No. 2014CB943003), and Hunan Provincial Innovation Foundation for Postgraduate 71380100016.

Conflict of interest

The authors declare that there are no conflict of interest.

Ethical standards

This research was approved by the University at Buffalo Institutional Animal Care and Use Committee. All applicable international, national, and institutional guidelines for the care and use of animals were followed.

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Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China

    Jintao Yu, Dalian Ding, Hong Sun & Richard Salvi

  2. Center for Hearing and Deafness, State University of New York at Buffalo, Buffalo, NY, 14214, USA

    Jintao Yu, Dalian Ding, Hong Sun & Richard Salvi

  3. Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, 14214, USA

    Jerome A. Roth

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  1. Jintao Yu
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  2. Dalian Ding
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Correspondence to Dalian Ding.

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Yu, J., Ding, D., Sun, H. et al. Neurotoxicity of Trimethyltin in Rat Cochlear Organotypic Cultures. Neurotox Res 28, 43–54 (2015). https://doi.org/10.1007/s12640-015-9531-2

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