Department of Audiology, University of Ferrara, Ferrara, Italy.
Med Sci Monit. 2011 Aug;17(8):BR179-186. doi: 10.12659/msm.881894.
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.
MATERIAL/METHODS: 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.
使用 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。每种潜在的化学保护剂在 3 种不同剂量下进行测试，以评估剂量对听觉保护的影响。
材料/方法：本研究共使用 40 只 Sprague-Dawley 白化雄性大鼠。动物分为 10 组，每组 3 个剂量的保护剂和一个顺铂处理的对照组。在药物暴露前对动物进行称重匹配，以确保所有组的体重相似。在治疗后 96 小时，使用听性脑干反应和畸变产物耳声发射评估听觉功能。
在治疗后随访时，D-蛋氨酸和 NAC 治疗组在 8 kHz 时没有发现明显的阈值变化。所有依布硒啉治疗组的动物均出现明显的阈值升高。在 12 和 16 kHz 时，只有接受 300、450 mg/kg D-蛋氨酸和 475 mg/kg NAC 治疗的组的阈值与治疗前 ABR 数据相当。依布硒啉治疗的动物出现明显的阈值移位，表现出最高的阈值升高。DPOAE 数据分析显示，只有 350 mg/kg D-蛋氨酸组的动物在治疗前后的记录之间没有统计学差异。
综合 ABR 和 DPOAE 分析的结果，只有 350 mg/kg D-蛋氨酸组在静脉注射 14 mg/kg 顺铂后表现出完全的听觉保护。依布硒啉预处理 Sprague-Dawley 白化雄性大鼠的数据表明，腹腔内给予高达 12 mg/kg 的依布硒啉在该物种中缺乏听觉保护。
