Yumusakhuylu Ali Cemal, Yazici Mine, Sari Murat, Binnetoglu Adem, Kosemihal Ebru, Akdas Ferda, Sirvanci Serap, Yuksel Meral, Uneri Cuneyd, Tutkun Alper
Marmara University, Faculty of Medicine, Otolaryngology Head&Neck Surgery,Turkey.
Int J Pediatr Otorhinolaryngol. 2012 Mar;76(3):404-8. doi: 10.1016/j.ijporl.2011.12.021. Epub 2012 Jan 18.
The aim of this study was to evaluate the effectiveness of systemic administration of resveratrol against cisplatin-induced ototoxicity in guinea pigs.
Healthy guinea pigs (n=24) were randomly divided into four groups. Group 1 (n=6) received resveratrol+cisplatin, group 2 (n=6) received 4% ethanol+cisplatin, group 3 (n=6) received cisplatin, and group 4 (n=6) received saline. Cisplatin was administered at a dose of 10mg/kg/day on days 14 and 15 of the study. Resveratrol (10mg/kg/day), 4% ethanol, and saline were administered throughout the study. Baseline auditory brainstem responses (ABR) (4 kHz, 8 kHz, and click stimulus) were determined for all groups. ABR was repeated 72 h after the last dose of cisplatin in order to record the threshold shifts. The ABR threshold shifts for the click stimulus, 4-kHz- and 8-kHz-frequency stimuli were compared after drug administration. After follow-up ABRs the animals sacrificed under deep sedation and their cochleae were removed. Left cochleae were immediately harvested for measurement of level of reactive oxygen species (ROS). Right cochleae were prepared for histological changes which were observed by scanning electron microscopy (SEM).
For the all stimulus, there was a significant threshold difference among the groups (p<0.01). Group 3 had a significantly higher threshold shift at all stimuli when compared with groups 1 and 4. There was no significant threshold shifts in all stimuli between groups 2 and 3. The resveratrol-treated group 1 showed preservation of threshold in ABR (p ≤ 0.05). SEM showed that inner and outer hair cells were preserved in the group 1. Level of reactive oxygen species (ROS) were significantly higher in groups 2 and 3 compared with groups 1 and 4 (p ≤ 0.05).
These results indicated that systemic administration of resveratrol afforded statistically significant protection to the cochlea of guinea pigs from cisplatin toxicity. Experimental dose of resveratrol injections may have a protective effect against cisplatin ototoxicity in guinea pigs.
本研究旨在评估白藜芦醇全身给药对顺铂诱导的豚鼠耳毒性的有效性。
将24只健康豚鼠随机分为四组。第1组（n = 6）接受白藜芦醇+顺铂，第2组（n = 6）接受4%乙醇+顺铂，第3组（n = 6）接受顺铂，第4组（n = 6）接受生理盐水。在研究的第14天和第15天，顺铂以10mg/kg/天的剂量给药。在整个研究过程中给予白藜芦醇（10mg/kg/天）、4%乙醇和生理盐水。测定所有组的基线听性脑干反应（ABR）（4kHz、8kHz和短声刺激）。在最后一剂顺铂给药72小时后重复ABR测定，以记录阈值变化。比较给药后短声刺激、4kHz和8kHz频率刺激的ABR阈值变化。随访ABR后，在深度镇静下处死动物并取出其耳蜗。立即收获左侧耳蜗以测量活性氧（ROS）水平。制备右侧耳蜗用于组织学变化观察，通过扫描电子显微镜（SEM）进行观察。
对于所有刺激，各组之间存在显著的阈值差异（p<0.01）。与第1组和第4组相比，第3组在所有刺激下的阈值变化显著更高。第2组和第3组在所有刺激下的阈值变化无显著差异。白藜芦醇治疗的第1组在ABR中显示阈值保留（p≤0.05）。SEM显示第1组的内、外毛细胞得以保留。与第1组和第4组相比，第2组和第3组的活性氧（ROS）水平显著更高（p≤0.05）。
这些结果表明，白藜芦醇全身给药对豚鼠耳蜗免受顺铂毒性具有统计学上的显著保护作用。实验剂量的白藜芦醇注射可能对豚鼠顺铂耳毒性具有保护作用。
Zotero 插件