Dose-dependent changes in the rat cochlea following aminoglycoside intoxication. I. Physiological study

Area of Science:

• Ototoxicology
• Auditory Neuroscience
• Pharmacology

Background:

• Amikacin is an aminoglycoside antibiotic used to treat severe bacterial infections.
• Aminoglycosides are known to cause ototoxicity, affecting the inner ear.
• Understanding the dose-dependent effects of amikacin is crucial for safe clinical use.

Purpose of the Study:

• To electrophysiologically evaluate the dose-dependent ototoxic effects of amikacin on the rat cochlea.
• To identify the specific auditory parameters affected by varying amikacin dosages.
• To correlate electrophysiological findings with potential anatomical changes.

Main Methods:

• Electrophysiological assessment using Compound Action Potential (CAP) audiograms, amplitude and latency-intensity curves, and CAP tuning curves.
• Subcutaneous administration of amikacin at doses ranging from 100 to 1000 mg/kg daily for five days.
• Testing conducted one month post-treatment to assess chronic effects.

Main Results:

• No ototoxicity observed at 100-200 mg/kg amikacin.
• Early changes (300-600 mg/kg) included CAP tuning curve alterations without threshold or latency shifts.
• Significant ototoxicity (≥800 mg/kg) manifested as increased CAP threshold and latency, disrupted amplitude-intensity function, and hyposensitive CAP tuning curves.

Conclusions:

• Amikacin exhibits dose-dependent ototoxicity in the rat cochlea.
• Electrophysiological measures can detect early and severe stages of amikacin-induced hearing damage.
• The findings provide a basis for understanding amikacin's impact on auditory function and correlate with anatomical studies.