Dose-dependent protection on cisplatin-induced ototoxicity - an electrophysiological study on the effect of three antioxidants in the Sprague-Dawley rat animal model.
Dose-dependent protection on cisplatin-induced ototoxicity - an electrophysiological study on the effect of three antioxidants in the Sprague-Dawley rat animal model.
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DOI：
10.12659/msm.881894
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Skarzynski H
中科院分区：
文献类型：
--
作者：
Lorito G;Hatzopoulos S;Laurell G;Campbell KC;Petruccelli J;Giordano P;Kochanek K;Sliwa L;Martini A;Skarzynski H
用Sprague-Dawley大鼠作为急性顺铂耳毒性模型，比较2种含硫抗氧化剂（D-蛋氨酸、N-L-乙酰半胱氨酸）和1种硒有机化合物（依布硒啉）的化学保护效果。以3种不同剂量测试每种推定的化学保护剂，以评估剂量对听觉保护的影响。本研究共使用40只Sprague-Dawley白化病雄性大鼠。将动物分为10组，每种保护剂的3个不同剂量组和顺铂处理的对照组。在药物暴露前对动物进行体重匹配，以确保所有组的体重相似。听觉功能进行了评估，听觉脑干反应和畸变产物耳声发射在时间零和96小时后治疗。在治疗后随访时，在D-Met和NAC治疗组中未发现8 kHz下的显著阈值变化。所有依布硒处理的动物均表现出显著的阈值升高。在12和16 kHz下，仅300、450 mg/kg D-Met和475 mg/kg NAC处理组的阈值与处理前ABR数据相当。依布硒处理的动物表现出显著的阈值偏移，并显示出最高的阈值升高。DPOAE数据分析显示，只有350 mg/kg D-met组的动物在记录前后没有统计学差异。综合考虑ABR和DPOAE分析的结果，仅350 mg/kg D-met组相对于14 mg/kg顺铂静脉内给药表现出完全的听觉保护。依布硒啉预处理Sprague-Dawley白化病雄性大鼠的数据表明，依布硒啉剂量高达12 mg/kg时，该物种缺乏听觉保护。
Sprague-Dawley rats were used as an acute cisplatin ototoxicity model to compare the chemo-protective efficacy of 2 sulphur-containing antioxidants (D-methionine, N-L-acetylcysteine) and 1 seleno-organic compound (ebselen). Each putative chemo-protective agent was tested at 3 different dosages in order to assess the influence of dose on auditory preservation. A total of 40 Sprague-Dawley albino male rats were used in the study. Animals were divided into 10 groups, 3 groups of different doses for each protective agent and a cisplatin-treated control group. The animals were weight-matched before drug exposure to ensure similar weights in all groups. Auditory function was assessed with auditory brainstem responses and distortion product otoacoustic emissions at time zero and at 96 hours post-treatment. At the post-treatment follow-up no significant threshold change at 8 kHz was found in the D-Met- and NAC-treated groups. All ebselen-treated animals presented significant threshold elevations. At 12 and 16 kHz, only the groups treated with 300, 450 mg/kg of D-Met and 475 mg/kg of NAC presented thresholds comparable to the pre-treatment ABR data. The ebselen-treated animals presented significant threshold shifts and showed the highest threshold elevations. The DPOAE data analysis showed that only the animals from the 350 mg/kg D-met group presented lack of statistical differences between the pre and post recordings. Considering the outcome from the ABR and DPOAE analyses together, only the 350 mg/kg D-met group presented a complete auditory preservation against the 14 mg/kg cisplatin administered i.v. Data from ebselen pre-treated Sprague-Dawley albino male rats demonstrate that ebselen dosages up to 12 mg/kg given by i.p. administration lack auditory preservation in this species.
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影响因子：
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作者：
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