Apoptosis in the OC-k3 immortalized cell line treated with different agents
L Bertolaso1, A Martini, D Bindini
1Center of Bioacoustics, Ferrara University, Italy.
Audiology : Official Organ of the International Society of Audiology
|January 10, 2002
Summary
Cisplatin and gentamicin induce inner ear cell death through apoptosis, driven by increased reactive oxygen species (ROS). Antioxidants effectively prevent this ototoxicity, suggesting ROS plays a key role in hearing loss.
Area of Science:
- Ototoxicity research
- Cellular apoptosis mechanisms
- Inner ear drug side effects
Background:
- Cochlear cells are vulnerable to drug-induced damage.
- Ototoxic drugs like cisplatin and gentamicin cause significant side effects.
- Understanding cell death mechanisms is crucial for mitigating hearing loss.
Purpose of the Study:
- To elucidate the mechanisms of cochlear cell death induced by ototoxic drugs.
- To investigate the role of reactive oxygen species (ROS) and glutathione (GSH) in drug-induced apoptosis.
- To evaluate the protective effects of antioxidants against ototoxicity.
Main Methods:
- Utilized an immortalized OC-k3 cell line derived from mouse organ of Corti.
- Exposed cells to varying concentrations of cisplatin and gentamicin over 48 hours.
- Assessed cell viability, ROS production, GSH levels, and apoptosis markers (nuclear fragmentation).
Main Results:
- Cisplatin and gentamicin induced dose- and time-dependent apoptosis in cochlear cells.
- Apoptosis was characterized by nuclear fragmentation with intact cell membranes and mitochondria.
- Early treatment showed increased ROS production and decreased GSH levels, linked to protein kinase C alpha activation.
Conclusions:
- Reactive oxygen species (ROS) generation is a key mechanism in drug-induced inner ear cell apoptosis.
- Antioxidants (N-acetylcysteine, GSH, vitamin C) significantly rescued cells from apoptosis.
- ROS may contribute to age-related hearing decline.
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