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Updated: Aug 19, 2026

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Minocycline prevents gentamicin-induced ototoxicity by inhibiting p38 MAP kinase phosphorylation and caspase 3
1Department of Neurology, School of Medicine, Indiana University, 975 West Walnut Street IB 457, Indianapolis, IN 46202, USA.
Abstract:
Aminoglycosides are commonly used antibiotics that often induce ototoxicity leading to permanent hair cell loss and hearing impairment. We hereby examined whether minocycline protects hair cells from gentamicin-induced hair cell damage. Two millimolar gentamicin significantly induced outer hair cell damage and the addition of minocycline to gentamicin-treated explants significantly increased hair cell survival in a dose-dependent manner. Additionally, we demonstrated that gentamicin induced p38 MAPK phosphorylation, cytochrome c release, and caspase 3 activation in these cells and these remarkable changes were blocked by minocycline treatments. Furthermore, we showed that the inhibitor of p38 MAPK or the inhibitor of caspase 3 only partially blocked gentamicin-induced hair cell damage, and the pretreatment of explants with the inhibitor of p38 MAPK and the inhibitor of caspase 3 together exerted a synergic protective effect against gentamicin-induced hair cell damage. Our results suggest that minocycline blocks gentamicin-induced hair cell loss possibly by inhibition of three mechanisms: p38 MAPK phosphorylation, cytochrome c release, and caspase 3 activation. This finding may explain why minocycline has protective activity in a variety of apoptotic models. Therapeutic intervention by using minocycline or related drugs may be a novel means for preventing inner ear injury following the use of aminoglycoside.
Insights
Minocycline protects against gentamicin-induced ototoxicity by preventing hair cell damage. This antibiotic may offer a novel therapeutic strategy for preventing aminoglycoside-induced inner ear injury.
Area of Science:
- Ototoxicity research
- Cellular and molecular biology
- Pharmacology
Background:
- Aminoglycosides are antibiotics frequently causing ototoxicity, leading to irreversible hearing loss.
- Ototoxicity results in hair cell damage and subsequent hearing impairment.
Purpose of the Study:
- To investigate the protective effects of minocycline against gentamicin-induced hair cell damage.
- To elucidate the molecular mechanisms underlying minocycline's protective action.
Main Methods:
- Utilized gentamicin to induce outer hair cell damage in explants.
- Administered minocycline in varying doses to assess its protective efficacy.
- Analyzed gentamicin-induced molecular changes, including p38 MAPK phosphorylation, cytochrome c release, and caspase 3 activation.
- Investigated the effects of specific inhibitors for p38 MAPK and caspase 3.
Main Results:
- Gentamicin significantly damaged outer hair cells.
- Minocycline treatment dose-dependently increased hair cell survival.
- Minocycline inhibited gentamicin-induced p38 MAPK phosphorylation, cytochrome c release, and caspase 3 activation.
- Inhibitors of p38 MAPK and caspase 3 provided partial protection, with combined inhibition showing a synergistic effect.
Conclusions:
- Minocycline protects hair cells from gentamicin-induced damage by inhibiting p38 MAPK phosphorylation, cytochrome c release, and caspase 3 activation.
- These findings suggest minocycline's potential as a therapeutic agent to prevent aminoglycoside-induced ototoxicity.
- Minocycline's protective activity may extend to other apoptotic models.
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