Takimoto Yasumitsu, Imai Takao, Kondo Makoto, Hanada Yukiko, Uno Atsuhiko, Ishida Yusuke, Kamakura Takefumi, Kitahara Tadashi, Inohara Hidenori, Shimada Shoichi
Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Otorhinolaryngology, Suita Municipal Hospital, 2-13-20 Katayama-cho, Suita City, Osaka 564-0082, Japan.
Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Toxicol Lett. 2016 Nov 16;262:49-54. doi: 10.1016/j.toxlet.2016.09.009. Epub 2016 Sep 19.
Cisplatin is a chemotherapeutic agent commonly used for the treatment of solid tumors, and its side-effects include vestibulotoxicity. Previous studies have reported cisplatin-induced vestibulotoxicity in various animal models, but no study has investigated in vivo mouse vestibular dysfunction after cisplatin. The aim of this study was to investigate cisplatin-induced vestibulotoxicity in C57BL/6J mice. Vestibular function was assessed by recording the vestibulo-ocular reflex (VOR). This was done during sinusoidal rotations in the horizontal plane at three frequencies (0.5, 1.0 and 2.5Hz). A high-resolution, high-frequency digital infra-red camera was used with eye-tracking algorithms. Cisplatin at 16mg/kg, but not 8mg/kg, decreased the VOR gain at 2.5Hz compared with the vehicle control. Following 16mg/kg cisplatin treatment, the animals showed no change in the optokinetic nystagmus response, suggesting that no major changes in visual or oculomotor functions had occurred. This mouse model may be useful for studying cisplatin-induced vestibulotoxicity and its treatment.
顺铂是一种常用于治疗实体瘤的化疗药物，其副作用包括前庭毒性。先前的研究已报道顺铂在各种动物模型中会引起前庭毒性，但尚无研究调查顺铂给药后小鼠体内的前庭功能障碍。本研究的目的是调查顺铂对C57BL/6J小鼠的前庭毒性。通过记录前庭眼反射（VOR）来评估前庭功能。这是在三个频率（0.5、1.0和2.5Hz）的水平面上进行正弦旋转时完成的。使用了配备眼动追踪算法的高分辨率、高频数字红外摄像机。与溶媒对照组相比，16mg/kg的顺铂（而非8mg/kg）降低了2.5Hz时的VOR增益。在接受16mg/kg顺铂治疗后，动物的视动性眼震反应没有变化，这表明视觉或眼球运动功能未发生重大改变。该小鼠模型可能有助于研究顺铂诱导的前庭毒性及其治疗方法。
