Bielefeld Eric C, Coling Donald, Chen Guang-Di, Henderson Donald
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.
J Negat Results Biomed. 2008 Jul 11;7:4. doi: 10.1186/1477-5751-7-4.
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.
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.
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).
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.
Fischer 344/NHsd大鼠从12个月大开始出现与年龄相关的、进行性的高频听力损失。这种损失与外毛细胞中的缺陷/死亡有关，而外毛细胞的缺陷/死亡又与线粒体产生的氧化应激有关。已知乙酰左旋肉碱（ALCAR）可增强线粒体生物能量学和膜效率。因此，ALCAR被视为一种可能的药物干预手段，用于预防甚至恢复衰老引起的听力损失。
采用三种不同的方案将ALCAR给予衰老的Fischer 344/NHsd大鼠。每种情况下的大鼠在治疗前、治疗期间和治疗后均通过听觉脑干反应评估听力。首先，给24个月大的大鼠腹腔注射ALCAR（100mg/kg，以25mg/ml溶解于生理盐水中），每天一次，持续一个月。其次，给18个月大的大鼠经口灌胃给予ALCAR（100mg/kg），持续90天。第三，给15个月大的大鼠经口灌胃给予ALCAR（100mg/kg），持续90天。每种情况下的对照大鼠通过腹腔注射或灌胃给予生理盐水。
在五种测试刺激（5、10、20和40kHz短音爆和一个咔嗒声）中的任何一种刺激下，三组接受ALCAR治疗的动物在治疗前、治疗期间或治疗后的听力阈值与匹配的对照组相比均无显著差异。
目前的研究没有提供证据表明，对Fischer 344/NHsd大鼠进行全身给药ALCAR可以改变其与年龄相关的听力损失。
