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Updated: Jan 8, 2026
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Restoring autophagy flux by rolipram attenuates ototoxicity in Hearing loss
Karthikeyan A Vijayakumar1, Chul Ho Jang2, Gwang-Won Cho3
1Department of Biological Science, College of Natural Sciences, Chosun University, 309, Gwangju, 61452, South Korea; The Basic Science Institute of Chosun University, Chosun University, Gwangju, 61452, South Korea.
Abstract:
Sensorineural hair cell loss is one of the major contributors to hearing loss. Failure of autophagy flux has been reported as a major factor that impairs hearing sense during various ototoxic conditions. In this study we investigated whether enhancing autophagy can mitigate kanamycin and furosemide induced cytotoxicity by using rolipram to restore the autophagy flux. Upon dose dependent treatment of kanamycin and furosemide, we observed depletion in the viability and impaired autophagy flux. Treatment with the PDE4 inhibitor rolipram restored autophagy activity and significantly improved cell survival. Consistent with an autophagy dependent mechanism, the protective effect of rolipram was abolished by chloroquine or Atg7 knockdown, confirming that intact autophagy flux is required for cellular protection. In vivo, rolipram attenuated kanamycin and furosemide induced hearing loss and preserved cochlear hair cells. Notably, ribbon synapses of inner hair cells were also maintained, indicating that autophagy enhancement protected both cellular integrity and synaptic function. These findings demonstrate that restoring autophagy flux represents a viable therapeutic strategy against ototoxic injury, and identify rolipram as a potential pharmacological agent for protecting auditory cells and hearing function.
Insights
Enhancing cellular autophagy flux with rolipram protects against hearing loss caused by ototoxic drugs like kanamycin and furosemide. This approach preserves auditory hair cells and synaptic function, offering a potential therapeutic strategy.
Area of Science:
- Ototoxicology
- Cellular Biology
- Neuroscience
Background:
- Sensorineural hair cell loss is a primary cause of hearing impairment.
- Impaired autophagy flux is linked to hearing dysfunction in ototoxic conditions.
Purpose of the Study:
- To investigate if enhancing autophagy can protect against kanamycin and furosemide-induced ototoxicity.
- To evaluate the potential of rolipram, a PDE4 inhibitor, in restoring autophagy flux and mitigating hearing loss.
Main Methods:
- Dose-dependent treatment of auditory cells with kanamycin and furosemide.
- Assessment of cell viability and autophagy flux.
- Treatment with rolipram to restore autophagy.
- Experimental validation using chloroquine and Atg7 knockdown.
- In vivo studies in animal models to assess hearing function and cochlear hair cell preservation.
Main Results:
- Kanamycin and furosemide reduced cell viability and impaired autophagy flux.
- Rolipram treatment restored autophagy activity and significantly improved cell survival.
- The protective effects of rolipram were dependent on intact autophagy flux.
- In vivo, rolipram reduced drug-induced hearing loss and preserved cochlear hair cells and ribbon synapses.
Conclusions:
- Restoring autophagy flux is a promising therapeutic strategy for ototoxic hearing injuries.
- Rolipram demonstrates potential as a pharmacological agent to protect auditory cells and hearing function.
