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Increased ototoxicity in both young and old mice
Archives of Otolaryngology (Chicago, Ill. : 1960)
|February 1, 1981
Summary
Infants are most susceptible to kanamycin ototoxicity, experiencing cochlear damage. Older mice also showed age-dependent hearing loss and hair cell damage, validating clinical observations.
Area of Science:
- Ototoxicology
- Auditory Neuroscience
- Pharmacology
Background:
- Aminoglycoside antibiotics, like kanamycin, are known to cause ototoxicity.
- Age-related susceptibility to ototoxicity is clinically observed but poorly understood at the molecular and cellular levels.
Purpose of the Study:
- To experimentally validate the age-dependent ototoxicity of kanamycin sulfate in mice.
- To establish an animal model for investigating the mechanisms of aminoglycoside-induced hearing loss across different age groups.
Main Methods:
- CBA/J mice of three age groups (preweanling, postadolescent, post-middle-aged) received kanamycin sulfate for two weeks.
- Functional assessment using electrocochleography to measure auditory nerve-evoked potential thresholds.
- Structural assessment via histocochleography to quantify hair cell loss in cochlea whole-mount preparations.
Main Results:
- Preweanling mice exhibited significant structural and functional cochlear losses across all regions.
- Postadolescent mice showed minimal functional loss and no structural damage.
- Older mice displayed basal hair cell loss and elevated high-frequency hearing thresholds.
Conclusions:
- Kanamycin sulfate ototoxicity is most severe in the youngest mice, supporting clinical observations in infants.
- Older mice demonstrate age-dependent susceptibility to kanamycin-induced hearing impairment and hair cell damage.
- This study provides a novel animal model for exploring age-related differences in aminoglycoside ototoxicity.