Institute of Otolaryngology, Catholic University School of Medicine, Largo Francesco Vito 1, 00168 Rome, Italy.
Neuroscience. 2010 Sep 15;169(4):1575-88. doi: 10.1016/j.neuroscience.2010.06.022. Epub 2010 Jun 20.
Ferulic acid (FA) is a phenolic compound whose neuroprotective activity was extensively studied in vitro. In this study, we provided functional in vivo evidence that FA limits noise-induced hearing loss. Guinea-pigs exposed to acoustic trauma for 1 h exhibited a significant impairment in auditory function; this injury was evident as early as 1 day from noise exposure and persisted over 21 days. Ferulic acid (150 mg/kg i.p. for 4 days) counteracted noise-induced hearing loss at days 1, 3, 7 and 21 from noise exposure. The improvement of auditory function by FA was paralleled by a significant reduction in oxidative stress, apoptosis and increase in hair cell viability in the organ of Corti. Interestingly in the guinea-pig cochleae, the neuroprotective effect of FA was functionally related not only to its scavenging ability in the peri-traumatic period but also to the up-regulation of the cytoprotective enzyme heme oxygenase-1 (HO-1); in fact, FA-induced improvement of auditory function was counteracted by the HO inhibitor zinc-protoporphyrin-IX and paralleled the time-course of HO-1 induction over 3-7 days. These results confirm the antioxidant properties of FA as free-radical scavenger and suggest a role of HO-1 as an additional mediator against noise-induced ototoxicity.
阿魏酸（FA）是一种酚类化合物，其神经保护活性在体外得到了广泛研究。在这项研究中，我们提供了功能上的体内证据，表明 FA 限制了噪声诱导的听力损失。暴露于声创伤 1 小时的豚鼠表现出明显的听觉功能障碍；这种损伤早在噪声暴露后 1 天就明显，并持续 21 天。阿魏酸（150mg/kg，腹腔注射，连续 4 天）在噪声暴露后 1、3、7 和 21 天对抗噪声诱导的听力损失。FA 改善听觉功能的同时，还显著降低了毛细胞在耳蜗中的氧化应激、细胞凋亡和活力。有趣的是，在豚鼠耳蜗中，FA 的神经保护作用不仅与其在创伤前时期的清除能力有关，而且与细胞保护酶血红素加氧酶-1（HO-1）的上调有关；事实上，FA 诱导的听觉功能改善被 HO 抑制剂锌原卟啉-IX 抵消，同时与 HO-1 诱导的时间过程平行，持续 3-7 天。这些结果证实了 FA 的抗氧化特性作为自由基清除剂，并表明 HO-1 作为对抗噪声诱导耳毒性的另一种介质的作用。
