Rybak Leonard P
Department of Surgery, Division of Otolaryngology, Southern Illinois University School of Medicine, PO Box 19653, Springfield, IL 62794-9653, USA.
Int Tinnitus J. 2005;11(1):23-30.
Platinum-containing drugs, such as cisplatin and carboplatin, are known to have ototoxic side effects causing hearing loss that may be accompanied by tinnitus. This study reviews recent studies on the ototoxicity of cisplatin and carboplatin and summarizes the effects of protective agents that may prevent hearing loss and tinnitus. The primary locus of ototoxicity is in the cochlea, but oxidative stress to the inferior colliculus has been reported recently with carboplatin. Enhanced spontaneous activity within the dorsal cochlear nucleus has been correlated with loss of outer hair cells in animal experiments using cisplatin. This may result from disinhibition of neurons within the dorsal cochlear nucleus caused by reduced input from spiral ganglion cells. Carboplatin may cause tinnitus by oxidative stress within the inferior colliculus or by loss of inhibition within the inferior colliculus resulting from cochlear damage. This could lead to compensatory gain and enhanced responses in neurons within the auditory cortex. Protective agents may prevent tinnitus by preventing damage to the cochlea, thereby obviating the development of disinhibition within central auditory pathways.
含铂药物，如顺铂和卡铂，已知具有耳毒性副作用，可导致听力丧失，可能伴有耳鸣。本研究回顾了近期关于顺铂和卡铂耳毒性的研究，并总结了可能预防听力丧失和耳鸣的保护剂的作用。耳毒性的主要部位在耳蜗，但最近有报道称卡铂会对下丘造成氧化应激。在使用顺铂的动物实验中，耳蜗背核内增强的自发放电活动与外毛细胞的损失相关。这可能是由于螺旋神经节细胞输入减少导致耳蜗背核内神经元的去抑制所致。卡铂可能通过下丘内的氧化应激或耳蜗损伤导致的下丘内抑制丧失而引起耳鸣。这可能导致听觉皮层内神经元的代偿性增益和反应增强。保护剂可能通过防止对耳蜗的损伤来预防耳鸣，从而避免中枢听觉通路内去抑制的发展。
