title: Multiple dosing strategies with acetyl L-carnitine (ALCAR) fail to alter age-related hearing loss in the Fischer 344/NHsd rat.
abstract: BACKGROUND
  The Fischer 344/NHsd rat undergoes age-related, progressive, high-frequency hearing loss beginning at age 12 months. The loss has been linked to defects/death in the outer hair cells related to oxidative stress originating in the mitochondria. Acetyl L-carnitine (ALCAR) is known to enhance mitochondrial bioenergetics and membrane efficiency. Therefore, ALCAR was targeted as a possible pharmacologic intervention to prevent, or even restore, hearing loss from aging.
  
  
  METHODS
  Three different paradigms were used to deliver ALCAR to aging Fischer 344/NHsd rats. Rats in each condition had their hearing evaluated by auditory brainstem responses before, during, and after treatment. First, 24-month-old rats were given ALCAR (100 mg/kg dissolved 25 mg/ml in saline) by IP injection daily for one month. Second, 18-month-old rats were given ALCAR (100 mg/kg) by oral gavage for 90 days. Third, 15-month-old rats were given ALCAR (100 mg/kg) by oral gavage for 90 days. Control rats in each condition received saline by i.p. injection or gavage.
  
  
  RESULTS
  Hearing thresholds of the three sets of ALCAR-treated animals were never significantly different from their matched controls before, during, or after the treatments at any of the five test stimuli (5, 10, 20, and 40 kHz tone bursts and a click).
  
  
  CONCLUSIONS
  The current study does not provide evidence that age-related hearing loss in the Fischer 344/NHsd rat can be altered with systemic administration of ALCAR.
authors.affiliation: Center for Hearing and Deafness, Department of Communicative Disorders and Sciences, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA. ecb2@buffalo.edu
authors.forename: Eric C
authors.initials: EC
authors.lastname: Bielefeld
authors.forename: Donald
authors.initials: D
authors.lastname: Coling
authors.forename: Guang-Di
authors.initials: GD
authors.lastname: Chen
authors.forename: Donald
authors.initials: D
authors.lastname: Henderson
mesh_terms: D000108:Acetylcarnitine / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D000375:Aging / Q000187:drug effects; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D034381:Hearing Loss / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000108:Acetylcarnitine