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Updated: Jun 22, 2026
The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
Differential protein expression profiles in salicylate ototoxicity of the mouse cochlea
Hak Hyun Jung1, Hyung Jin Kim, Gi Jung Im
1Department of Otolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Republic of Korea. ranccoon@naver.com
Abstract:
The purpose of this study was to investigate protein expression profiles of salicylate ototoxicity using proteomic analysis, and to identify whether salicylates induce apoptosis in organotypic culture of mouse cochlear cells. The adult mice were injected intraperitoneally with 400mg/kg of sodium salicylate. Approximately 30dB threshold shift was observed 3h after the injection, and the hearing threshold returned to normal range within 3 days. Proteomic analysis of mouse cochlea was performed 3h after salicylate injection, because this was the time to show maximal ototoxic effect in salicylate intoxication. Expression pattern of proteomic analysis at 3h was compared with those of normal cochlea and cochlea 3 days after salicylate injection. Sixteen proteins were transiently up-regulated threefolds or more at 3h after the injection compared with normal cochlea, and three proteins were down-regulated at 3h. Similar protein expression profiles were also observed between normal and 3 days group. These up-regulated and down-regulated proteins at 3h were analyzed by MALDI-TOF MS. The mRNA expressions of nine selected genes from 16 up-regulated protein profiles were also investigated by RT-PCR, and their expression levels at 3h were found to be higher than those of normal cochlea. We also confirmed the ototoxicity of salicylate in organotypic culture of cochlear cells using MTT assay, Hoechst staining and DNA laddering assay in vitro, and found that salicylate decreased the viability of cells in a time and dose-dependent manner, and that induced apoptosis in organotypic culture of cochlear cells. This study demonstrated that some proteins can be related to salicylate ototoxicity, and provides basic information about candidate proteins which are related to pathologic changes in salicylate-induced ototoxicity.
Insights
Salicylate ototoxicity in mice involves temporary hearing loss and altered protein expression in the cochlea. This study identifies specific proteins linked to salicylate-induced apoptosis in mouse cochlear cells.
Area of Science:
- Oto-toxicology
- Proteomics
- Molecular Biology
Background:
- Salicylates are known to cause ototoxicity, manifesting as temporary hearing loss.
- The molecular mechanisms underlying salicylate-induced ototoxicity, particularly protein expression changes and apoptosis, require further investigation.
Purpose of the Study:
- To investigate protein expression profiles associated with salicylate ototoxicity using proteomic analysis.
- To determine if salicylates induce apoptosis in organotypic cultures of mouse cochlear cells.
Main Methods:
- Adult mice received intraperitoneal injections of sodium salicylate (400mg/kg).
- Proteomic analysis (MALDI-TOF MS) and mRNA expression analysis (RT-PCR) were performed on cochlear tissues at 3 hours and 3 days post-injection.
- In vitro studies utilized MTT assay, Hoechst staining, and DNA laddering to assess apoptosis in cochlear cell cultures.
Main Results:
- A transient 30dB threshold shift in hearing was observed 3 hours after salicylate injection, returning to normal within 3 days.
- Proteomic analysis revealed 16 proteins transiently up-regulated and 3 down-regulated at 3 hours post-injection compared to normal cochlea.
- Salicylate exposure decreased cochlear cell viability and induced apoptosis in a time- and dose-dependent manner in vitro.
Conclusions:
- Specific protein expression changes are associated with salicylate ototoxicity.
- Salicylates induce apoptosis in mouse cochlear cells, suggesting a mechanism for salicylate-induced hearing damage.
- This study provides candidate proteins involved in the pathological changes of salicylate-induced ototoxicity.
