D-methionine (D-met) significantly reduces kanamycin-induced ototoxicity in pigmented guinea pigs

Abstract

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.

Key Words:

• Aminoglycoside
• D-methionine
• kanamycin
• ototoxicity
• otoprotection

Acknowledgements

This research was funded by NIH/NIDCD: 3R01DC0,08412–03S1.

Declaration of interest

Dr. Kathleen Campbell is the sole inventor on the patents for D-methionine as a protective agent. All of her patents are owned by her employer, Southern Illinois University School of Medicine. Since the study was completed, she has become the cofounder of MetArmor, a biotechnology company founded on otoprotection. Dr. Daniel Fox is also collaborating with the MetArmor team, however he does not have any financial affiliations. All other authors do not have personal relationships with organizations that could potentially be perceived as influencing the described research. All authors have read the journal’s disclosure policy of potential conflicts of interest.