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.

Prevention of treatment-induced ototoxicity: An update for clinicians

“…Pharmacological agents such as D-methionine have been shown to exhibit otoprotective benefits and therefore hold much potential. [17] Expression of certain neurotrophins in cochlear hair cells and neurotrophin receptors, selective tyrosine kinase receptor B (TrkB) and C (TrkC) and the low-affinity p75 receptor (a member of the tumour necrosis factor superfamily of receptors) in the spiral ganglion neurons, has been revealed. [18] Otoprotective agents can be aimed at protecting patients with normal auditory-vestibular function at the start of treatment, while neurotrophins can be an intervention that targets restoration.…”

Pediatric Ototoxicity: Current Trends and Management

“…Extensive work in otoprotectant agents to reduce occurrence and severity of chemotherapy-induced hearing loss (and noise-induced hearing loss) has been underway for decades. 18 To compare across multiple clinical trial sites, and across multiple studies, outcomes must be uniform. If a safe and effective otoprotective agent could be identified, oncologists may be able to treat the cancer more aggressively without hearing loss consequences.…”

Charge Trapping in Mixed Organic Donor–Acceptor Semiconductor Thin Films

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transient spectroscopy, [ 16,17 ] transient photocurrent, [ 18 ] and thermally stimulated current. [ 19,20 ] It has been found that trapping is strongly dependent on the particular combination of D-A molecules and illumination conditions employed.

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“…However, the important problem of the dependence of charge trapping on the content and concentration of D-A mixtures and on fi lm morphology has not yet been thoroughly investigated. Indeed, previous investigations have provided the density of gap states and/or trap site densities; [15][16][17][18][19][20] but, to our knowledge, a quantitative determination of the relationship between OPV performance and the density of trapped charges has not been reported.Using the experimental set up in Figure 1 , we illuminate the sample under investigation by a relatively intense, high-energy optical pump that generates excitons that subsequently dissociate into free charges (i.e., polarons). These charges result in a photocurrent ( I p ), while a small fraction populate trap states within the organic energy gap.…”

“…However, the important problem of the dependence of charge trapping on the content and concentration of D-A mixtures and on fi lm morphology has not yet been thoroughly investigated. Indeed, previous investigations have provided the density of gap states and/or trap site densities; [15][16][17][18][19][20] but, to our knowledge, a quantitative determination of the relationship between OPV performance and the density of trapped charges has not been reported.…”