Related Experiment Video
Updated: Sep 29, 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
Age-related sensitivity to cisplatin ototoxicity in gerbils
K C Sie1, L M deSerres, S J Norton
1Children's Hospital and Regional Medical Center, and Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle 98105, USA. ksie@chmc.org
Insights
Gerbils exposed to cisplatin during development show varying sensitivity to ototoxicity. Maximal hearing damage from cisplatin occurs in young gerbils, indicating a critical developmental window for this side effect.
Area of Science:
- Ototoxicity research
- Developmental neuroscience
- Pharmacology
Background:
- Cisplatin is a widely used chemotherapy agent.
- Ototoxicity is a known dose-limiting side effect of cisplatin.
- The developmental period of maximal sensitivity to cisplatin ototoxicity is not well-defined.
Purpose of the Study:
- To determine the developmental period of maximal sensitivity to cisplatin-induced ototoxicity in gerbils.
- To investigate the impact of cisplatin exposure at different post-natal ages on auditory function.
Main Methods:
- Five groups of gerbils were exposed to cisplatin at different post-natal ages (P10, P14, P18, P22, P42).
- Distortion product otoacoustic emissions (DPOAEs) were measured at 45 days of age.
- Distortion product grams and input-output functions were analyzed.
- A secondary analysis compared cisplatin-exposed P14 gerbils with saline-treated controls.
Main Results:
- A statistically significant difference in DPOAEs was observed between gerbils exposed at P14 and P42.
- A significant interaction between age and frequency was found in the P14 group.
- Cisplatin exposure in P14 gerbils resulted in a significant treatment effect on DPOAE levels compared to controls.
Conclusions:
- Age significantly influences cisplatin ototoxicity in gerbils.
- Frequency affects DPOAE levels in P14 gerbils exposed to cisplatin.
- These findings support a 'sensitive' developmental period for cisplatin ototoxicity in gerbils.
Abstract:
This study was undertaken to define the developmental period of maximal sensitivity to cisplatin ototoxicity in gerbils. Five groups were established based upon post-natal age (P) at exposure to cisplatin, P10 (n = 8), P14 (n = 8), P18 (n = 6), P22 (n = 7) and P42 (n = 7). Animals were given cisplatin, 1 mg/kg/day intraperitoneal for 4 days. In the first four groups, P10, P14, P18 and P22, distortion product otoacoustic emissions were measured at 45 days of age, when responses were expected to be developmentally stable. Distortion product grams and input-output functions were measured. There was a statistically significant difference only between P14 and P42 (P<0.01). There was a significant interaction of age and frequency in the P14 group only (P<0.01). A secondary analysis compared distortion product grams of P14 animals, exposed to cisplatin, and age-matched saline-treated animals (n = 6). There was a significant treatment effect. In summary, there was an effect of age on the cisplatin ototoxicity in gerbils. Also, there was an effect of the frequency on DPOAE levels in P14 gerbils. These data support the presence of a 'sensitive' period to cisplatin ototoxicity in gerbils.
