Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China.
Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China; Institute of Eye and ENT, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China.
Neuropharmacology. 2017 Apr;116:429-440. doi: 10.1016/j.neuropharm.2017.01.001. Epub 2017 Jan 3.
Cisplatin is a broad-spectrum anticancer drug that is commonly used in the clinic. Ototoxicity is one of the major side effects of this drug, which caused irreversible sensorineural hearing loss. Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-apoptotic and anti-oxidative activities in vitro and in vivo studies. We took advantage of C57 mice intraperitoneally injected with cisplatin alone or with cisplatin and allicin combined, to investigate whether allicin plays a protective role in vivo against cisplatin ototoxicity. The result showed that C57 mice in cisplatin group exhibited increased shift in auditory brainstem response, whereas the auditory fuction of mice in allicin + cisplatin group was protected in most frequencies, which was accordance with observed damages of outer hair cells (OHCs) and spiral ganglion neurons (SGNs) in the cochlea. Allicin markedly protected SGN mitochondria from damage and releasing cytochrome c, and significantly reduced pro-apoptosis factor expressions activated by cisplatin, including Bax, cleaved-caspase-9, cleaved-caspase-3and p53. Furthermore, allicin reduced the level of Malondialdehyde (MDA), but increased the level of superoxide dismutase (SOD). All data suggested that allicin could prevent hearing loss induced by cisplatin effectively, of which allicin protected SGNs from apoptosis via mitochondrial pathway while protected OHCs and supporting cells (SCs) from apoptosis through p53 pathway.
顺铂是一种广谱抗癌药物，临床上常用。耳毒性是该药物的主要副作用之一，可导致不可逆的感觉神经性听力损失。大蒜中的主要生物活性化合物大蒜素，已被证明在体外和体内研究中具有多种抗凋亡和抗氧化作用。我们利用腹腔注射顺铂的 C57 小鼠，单独或联合使用顺铂和大蒜素，研究大蒜素在体内是否对顺铂耳毒性具有保护作用。结果表明，顺铂组的 C57 小鼠听性脑干反应（ABR）潜伏期明显延长，而大蒜素+顺铂组的大多数频率的听力功能均得到保护，这与耳蜗外毛细胞（OHCs）和螺旋神经节神经元（SGNs）的损伤观察结果一致。大蒜素可显著保护 SGN 线粒体免受损伤和细胞色素 c 的释放，并显著降低顺铂激活的促凋亡因子的表达，包括 Bax、cleaved-caspase-9、cleaved-caspase-3 和 p53。此外，大蒜素降低了丙二醛（MDA）的水平，但增加了超氧化物歧化酶（SOD）的水平。所有数据表明，大蒜素能有效预防顺铂引起的听力损失，其通过线粒体途径保护 SGN 免于凋亡，通过 p53 途径保护 OHCs 和支持细胞（SCs）免于凋亡。
