Huang Xinyan, Whitworth Craig A, Rybak Leonard P
Division of Otolaryngology Head & Neck Surgery, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9662, USA.
Otol Neurotol. 2007 Sep;28(6):828-33. doi: 10.1097/mao.0b013e3180430163.
A standardized Ginkgo biloba extract, EGb 761, may have protective effect against cisplatin-induced ototoxicity in rats.
Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. Cisplatin-induced ototoxicity has been correlated to depletion of the cochlear antioxidant system and increased lipid peroxidation. EGb 761 contains potent antioxidants capable of scavenging free radicals, inhibiting nitric oxide synthesis, reducing lipid peroxidation, and protecting against apoptosis. The purpose of this study was to investigate the effect of EGb 761 on cisplatin-induced ototoxicity in rats.
Male Wistar rats were divided into four groups and were treated as follows: 1) vehicle control; 2) cisplatin (13 mg/kg, intraperitoneally) plus vehicle; 3) EGb 761 (200 mg/kg, intraperitoneally); and 4) EGb 761 plus cisplatin. Auditory brainstem responses (ABRs) were measured pretreatment and 72 hours posttreatment, and threshold shifts were analyzed. Endocochlear potentials (EPs) were also obtained at 72 hours posttreatment. Cochleae were harvested and processed for scanning electron microscopy after completion of auditory testing.
Cisplatin-treated rats showed significant ABR threshold shifts across all frequencies (click, and 2-, 4-, 8-, 16-, and 32-kHz tones) compared with each of the other groups (p < 0.001). Rats treated with EGb 761 plus cisplatin did not show significant ABR threshold shifts (p > 0.05). Similarly, the EPs of cisplatin-treated rats were decreased significantly approximately 50% in comparison with the other groups (p < 0.001). The EPs of EGb 761 plus cisplatin-treated rats were decreased less than 20% compared with vehicle control group or the EGb 761 only group (p < 0.01). The scanning electron microscopy observation indicated severe outer hair cell loss in the basal turn of cochleae of cisplatin-treated rats, whereas outer hair cells remained intact in the rats treated with EGb 761 plus cisplatin.
These results demonstrate that EGb 761 protects against cisplatin-induced ototoxicity.
标准化银杏叶提取物EGb 761可能对顺铂诱导的大鼠耳毒性具有保护作用。
顺铂诱导的耳毒性是抗癌化疗中的主要剂量限制性副作用。顺铂诱导的耳毒性与耳蜗抗氧化系统的消耗和脂质过氧化增加有关。EGb 761含有能够清除自由基、抑制一氧化氮合成、减少脂质过氧化和防止细胞凋亡的强效抗氧化剂。本研究的目的是探讨EGb 761对顺铂诱导的大鼠耳毒性的影响。
将雄性Wistar大鼠分为四组并进行如下处理：1）溶剂对照组；2）顺铂（13mg/kg，腹腔注射）加溶剂；3）EGb 761（200mg/kg，腹腔注射）；4）EGb 761加顺铂。在治疗前和治疗后72小时测量听性脑干反应（ABR），并分析阈值变化。在治疗后72小时也获得内耳蜗电位（EP）。在听觉测试完成后，收获耳蜗并进行扫描电子显微镜检查。
与其他各组相比，顺铂治疗的大鼠在所有频率（咔嗒声以及2、4、8、16和32kHz音调）上均表现出显著的ABR阈值变化（p < 0.001）。用EGb 761加顺铂治疗的大鼠未表现出显著的ABR阈值变化（p > 0.05）。同样，与其他组相比，顺铂治疗的大鼠的EP显著降低约50%（p < 0.001）。与溶剂对照组或仅用EGb 761治疗的组相比，用EGb 761加顺铂治疗的大鼠的EP降低不到20%（p < 0.01）。扫描电子显微镜观察表明，顺铂治疗的大鼠耳蜗基底转中外毛细胞严重丢失，而用EGb 761加顺铂治疗的大鼠中外毛细胞保持完整。
这些结果表明EGb 761可预防顺铂诱导的耳毒性。
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