Assessment of D-methionine protecting cisplatin-induced otolith toxicity by vestibular-evoked myogenic potential tests, ATPase activities and oxidative state in guinea pigs

作者：Lo Wu Chia; Chang Chih Ming; Liao Li Jen; Wang Chi Te; Young Yi Ho; Chang Yih Leong^*; Cheng Po Wen

来源：Neurotoxicology and Teratology, 2015, 51: 12-20.

DOI：10.1016/j.ntt.2015.07.004

• Bone-conducted vibration
• Vestibular-evoked myogenic potential
• D-Methionine
• Lipid peroxidation
• Nitric oxide

To date, inadequate study has been devoted to the toxic vestibular effects caused by cisplatin. In addition, no electrophysiological examination has been conducted to assess cisplatin-induced otolith toxicity. The purposes of this study are thus two-fold: 1) to determine whether cervical vestibular-evoked myogenic potentials (VEMPs) and ocular VEMPs are practical electrophysiological methods of testing for cisplatin-induced otolith toxicity and 2) to examine if D-methionine (D-met) pre-injection would protect the otolith organs against cispladn-induced changes in enzyme activities and/or oxidative status. Guinea pigs were intraperitoneally treated once daily with the following injections for seven consecutive days: sterile 0.9% saline control, cisplatin (5 mg/kg) only, D-met (300 mg/kg) only, or a combination of D-met (300 mg/kg) and cisplatin (5 mg/kg), respectively, with a 30 minute window in between. Each animal underwent the oVEMP and cVEMP tests before and after treatment. The changes in the biochemistry of the otolith organs, including membranous Na+, K+-ATPase and Ca2+-ATPase, lipid peroxidation (LPO) levels and nitric oxide (NO) levels, were also evaluated. In the cisplatin-only treated guinea pigs, the mean amplitudes of the oVEMP tests were significantly (p < 0.05) decreased when compared to the other three groups. In guinea pigs receiving both D-met and cisplatin, the amplitudes of their oVEMP tests were significantly larger (p < 0.05) than those of the cisplatin-only group, but smaller (p < 0.05) than those of the saline control or D-met-only group. However, no significant difference of the amplitudes of cVEMP tests was noted among the four groups. In comparison with the other three groups, the cisplatin-only group had the lowest (ps <0.05) mean Na+, K+-ATPase and Ca2+-ATPase, and the highest (ps < 0.05) LPO and NO levels. The oVEMP tests were feasible for the evaluation of cisplatin-related otolith dysfunction. D-Met attenuated the reduced ATPase activities and increased oxidative stress induced by cisplatin toxicity in the otolith organs.

• 出版日期2015-10