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. 2008 Jul 11:7:4.
doi: 10.1186/1477-5751-7-4.

Multiple dosing strategies with acetyl L-carnitine (ALCAR) fail to alter age-related hearing loss in the Fischer 344/NHsd rat

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Multiple dosing strategies with acetyl L-carnitine (ALCAR) fail to alter age-related hearing loss in the Fischer 344/NHsd rat

Eric C Bielefeld et al. J Negat Results Biomed. .

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).

Conclusion: 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.

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Figures

Figure 1
Figure 1
Data from the study of F344/NHsd rats starting at 15 months of age. Mean ABR thresholds in response to 5, 10, 20, and 40 kHz tone burst stimuli, as well as a click stimulus are displayed for rats aged 15 (dark and open circle symbols) and 18 months (dark and open triangle symbols). 9 animals were treated for three months with ALCAR (dark circle and dark triangle symbols); 9 were treated with saline as controls (open circle and triangle symbols). Error bars are +/- 1 standard deviation.
Figure 2
Figure 2
Data from the study of F344/NHsd rats starting at 18 months of age. Mean ABR thresholds in response to 5, 10, 20, and 40 kHz tone burst stimuli, as well as a click stimulus are displayed for rats aged 18 (Top Panel), 21 months (Middle Panel), and 23 months (Bottom Panel). 9 animals were treated for three months with ALCAR (dark circle symbols); 9 were treated with saline as controls (open circle symbols). Error bars are +/- 1 standard deviation.
Figure 3
Figure 3
Data from the study of F344/NHsd rats starting at 24 months of age. Mean ABR thresholds in response to 5, 10, 20, and 40 kHz tone burst stimuli, as well as a click stimulus are displayed for rats aged 25 months. 4 animals were treated for one month from age 24 months to age 25 months with ALCAR (dark circle symbols); 4 were treated with saline as controls (open circle symbols). Error bars are +/- 1 standard deviation.

References

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