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白藜芦醇对顺铂耳毒性的预防作用。

The effect of resveratrol on the prevention of cisplatin ototoxicity.

机构信息

Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, İnonu University, Malatya, Turkey.

出版信息

Eur Arch Otorhinolaryngol. 2012 Oct;269(10):2185-8. doi: 10.1007/s00405-011-1883-5. Epub 2011 Dec 21.

DOI:10.1007/s00405-011-1883-5
PMID:22186767
Abstract

One of the most important adverse effects of cisplatin, a chemotherapeutic agent which is widely used in the treatment of cancer patients, is hearing loss. This has primarily been associated with the loss of inner ear hairy and spiral ganglion cells due to oxidative stress. Resveratrol is known to be an antioxidant agent, which has the theoretical potential of preventing cisplatin-related ototoxicity. This experimental study was approved by Animal Ethics Committee of Inonu University (2008-20) and supported by Inonu University Scientific Research Projects Support Fund (2009-17). Thirty-four 3-month-old Wistar albino female rats weighing 210-270 g were used in the study. The animals were allocated into four groups: in cisplatin group (Group A), a single dose of 12 mg/kg cisplatin was administered intraperitoneally to 10 rats; in cisplatin + resveratrol group (Group B), a single dose of 12 mg/kg cisplatin and 10 mg/kg resveratrol were administered intraperitoneally for 5 days to 10 rats; in resveratrol group (Group C), 10 mg/kg resveratrol was administered intraperitoneally for 5 days to seven rats and in control group (Group D), resveratrol solvent (5% alcohol-95% physiological saline) was administered intraperitoneally for 5 days to seven rats. Resveratrol administration has begun 1 day before cisplatin administration in the group treated with cisplatin and resveratrol combination. Distortion product otoacoustic emission (DPOAE) (Grason Stadler, Madison, USA) measurements were performed in the same ear of all rats (right ear) under general anesthesia at baseline, 1st and 5th days after drug administration. Statistically significant distortion product amplitude reductions were found in the cisplatin group at 1,418, 2,003, 3,363, 5,660, 8,003 and 9,515 Hz frequencies. Whereas in the cisplatin + resveratrol group, statistically significant difference was found between 1st and 5th day measurements only at 3,996 Hz frequency. No significant differences were noted between the measurements either in the resveratrol or in the control groups. According to these results, cisplatin-related ototoxicity has been greatly prevented by resveratrol use.

摘要

顺铂是一种广泛用于癌症患者治疗的化疗药物,其最重要的不良反应之一是听力损失。这主要与内耳毛细胞和螺旋神经节细胞因氧化应激而丧失有关。白藜芦醇是一种抗氧化剂,具有预防顺铂相关性耳毒性的理论潜力。这项实验研究得到了因纽努大学动物伦理委员会(2008-20)的批准,并得到了因纽努大学科学研究项目支持基金(2009-17)的支持。研究使用了 34 只 3 个月大、体重 210-270 克的 Wistar 白化雌性大鼠。这些动物被分为四组:顺铂组(A 组),10 只大鼠腹腔注射 12mg/kg 顺铂;顺铂+白藜芦醇组(B 组),10 只大鼠腹腔注射 12mg/kg 顺铂和 10mg/kg 白藜芦醇 5 天;白藜芦醇组(C 组),7 只大鼠腹腔注射 10mg/kg 白藜芦醇 5 天;对照组(D 组),7 只大鼠腹腔注射白藜芦醇溶剂(5%酒精-95%生理盐水)5 天。在联合使用顺铂和白藜芦醇的组中,白藜芦醇的给药在顺铂给药前 1 天开始。所有大鼠(右耳)均在全身麻醉下于基线、药物给药后第 1 天和第 5 天进行畸变产物耳声发射(DPOAE)(Grason Stadler,Madison,USA)测量。在顺铂组中,在 1、418、2、003、3、363、5、660、8、003 和 9、515Hz 频率下,畸变产物幅度明显降低。而在顺铂+白藜芦醇组中,仅在 3、996Hz 频率下,第 1 天和第 5 天的测量值之间存在统计学差异。在白藜芦醇组或对照组中,测量值之间没有显著差异。根据这些结果,白藜芦醇的使用极大地预防了顺铂相关性耳毒性。

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