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Cisplatin: evaluation of its ototoxic potential
American Journal of Otolaryngology
|July 1, 1986
Summary
Cisplatin causes significant inner ear damage, including hair cell degeneration, even at low doses in an organ culture model. While highly ototoxic in vitro, clinical ototoxicity is less severe than with aminoglycosides due to dosing schedules.
Area of Science:
- Ototoxicology
- Inner Ear Biology
- Pharmacology
Background:
- Cisplatin is a potent chemotherapy agent with known ototoxic side effects.
- Understanding the dose-dependent ototoxicity of cisplatin is crucial for patient management.
Purpose of the Study:
- To evaluate the ototoxic potential of cisplatin in an in vitro organ culture model.
- To determine the specific effects of varying cisplatin concentrations on inner ear structures.
Main Methods:
- Organ culture model of inner ear structures.
- Exposure to cisplatin at concentrations ranging from 0.1 to 10 micrograms/ml.
- Morphological analysis of hair cells and supporting cells at the ultrastructural level.
Main Results:
- Selective hair cell degeneration observed at 0.1 microgram/ml.
- Morphologic damage to supporting cells occurred at 1 microgram/ml.
- Total collapse of the membranous labyrinth at 10 micrograms/ml over five days.
- Ultrastructural degeneration patterns were nonspecific, with chromatin changes.
Conclusions:
- Cisplatin exhibits significant ototoxicity in the studied in vitro model, exceeding that of aminoglycosides at equivalent concentrations.
- Despite high in vitro ototoxicity, clinical ototoxicity is mitigated by cisplatin's dosing regimen compared to aminoglycosides.