title: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: a Department of Medical Microbiology, Immunology, and Cell Biology , Southern Illinois University School of Medicine , Springfield , USA and.
authors.forename: Kathleen C M
authors.initials: KC
authors.lastname: Campbell
authors.affiliation: a Department of Medical Microbiology, Immunology, and Cell Biology , Southern Illinois University School of Medicine , Springfield , USA and.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Martin
authors.affiliation: a Department of Medical Microbiology, Immunology, and Cell Biology , Southern Illinois University School of Medicine , Springfield , USA and.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Meech
authors.affiliation: a Department of Medical Microbiology, Immunology, and Cell Biology , Southern Illinois University School of Medicine , Springfield , USA and.
authors.forename: Tim L
authors.initials: TL
authors.lastname: Hargrove
authors.affiliation: b Statistics and Research Consulting , Southern Illinois University School of Medicine , Springfield , USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Verhulst
authors.affiliation: a Department of Medical Microbiology, Immunology, and Cell Biology , Southern Illinois University School of Medicine , Springfield , USA and.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fox
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000517:prevention & control*; D007612:Kanamycin / Q000009:adverse effects*; D008297:Male; D008715:Methionine / Q000008:administration & dosage*; D020011:Protective Agents / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D020011:Protective Agents; D007612:Kanamycin; D008715:Methionine
keywords: Aminoglycoside; D-methionine; kanamycin; otoprotection; ototoxicity