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Updated: Mar 24, 2026
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
D-methionine (D-met) significantly reduces kanamycin-induced ototoxicity in pigmented guinea pigs
Kathleen C M Campbell1, Seth M Martin1, Robert P Meech1
1a Department of Medical Microbiology, Immunology, and Cell Biology , Southern Illinois University School of Medicine , Springfield , USA and.
Objective:
Test D-methionine (D-met) as an otoprotectant from kanamycin-induced ototoxicity and determine the lowest maximally protective D-met dose.
Design:
Auditory brainstem responses (ABR) were measured at 4, 8, 14, and 20 kHz at baseline and two, four, and six weeks after kanamycin and D-met administration initiation. ABR threshold shifts assessed auditory function. Following six-week ABR testing, animals were decapitated and cochleae collected for outer hair cell (OHC) quantification.
Study Sample:
Eight groups of 10 male pigmented guinea pigs were administered a subcutaneous kanamycin (250 mg/kg/dose) injection once per day and an intraperitoneal D-met injection (0 (saline), 120, 180, 240, 300, 360, 420, or 480 mg/kg/day) twice per day for 23 days.
Results:
Significant ABR threshold shift reductions and increased OHC counts (p ≤ 0.01) were measured at multiple D-met-dosed groups starting at two-week ABR assessments. A 300 mg/kg/day optimal otoprotective D-met dose provided 34-41 dB ABR threshold shift reductions and OHC protection. Lesser, but significant, D-met otoprotection was measured at lower and higher D-met doses.
Conclusions:
D-met significantly reduced ABR threshold shifts and increased OHC percentages compared to kanamycin-treated controls. Results may be clinically significant particularly for multidrug-resistant tuberculosis patients who frequently suffer from kanamycin-induced hearing loss in developing countries.
Insights
D-methionine (D-met) protects against kanamycin-induced hearing loss by reducing auditory brainstem response (ABR) threshold shifts and preserving outer hair cells (OHCs). The optimal protective dose was found to be 300 mg/kg/day.
Area of Science:
- Ototoxicity research
- Pharmacology of amino acids
- Auditory neuroscience
Background:
- Kanamycin is an aminoglycoside antibiotic known to cause ototoxicity, leading to hearing loss.
- Hearing loss is a significant side effect, particularly in patients treated for multidrug-resistant tuberculosis.
- D-methionine (D-met) is an amino acid isomer with potential therapeutic properties.
Purpose of the Study:
- To evaluate D-methionine (D-met) as a protective agent against kanamycin-induced ototoxicity.
- To determine the lowest effective dose of D-met for otoprotection.
- To assess the impact of D-met on auditory function and cochlear hair cell survival.
Main Methods:
- Guinea pigs received daily kanamycin injections and varying doses of D-met for 23 days.
- Auditory brainstem responses (ABR) were measured at multiple frequencies over six weeks to assess hearing function.
- Outer hair cell (OHC) counts were quantified in cochlear samples post-treatment.
Main Results:
- D-methionine administration significantly reduced ABR threshold shifts and increased OHC counts compared to controls.
- The optimal otoprotective dose of D-met was identified as 300 mg/kg/day, yielding 34-41 dB ABR threshold shift reductions.
- Significant otoprotection was observed across multiple D-met doses, indicating a dose-dependent protective effect.
Conclusions:
- D-methionine effectively mitigates kanamycin-induced ototoxicity, preserving both auditory function and cochlear hair cells.
- The findings suggest D-met may be a valuable therapeutic adjunct for patients at risk of kanamycin-induced hearing loss.
- Clinical significance is highlighted for patients with multidrug-resistant tuberculosis, a population often experiencing kanamycin-related hearing impairment.
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