Kilic Korhan, Sakat Muhammed Sedat, Akdemir Fazile Nur Ekinci, Yildirim Serkan, Saglam Yavuz Selim, Askin Seda
Ataturk University, Faculty of Medicine, Department of Otorhinolaryngology, Erzurum, Turkey.
Ataturk University, Faculty of Medicine, Department of Otorhinolaryngology, Erzurum, Turkey.
Braz J Otorhinolaryngol. 2019 May-Jun;85(3):267-274. doi: 10.1016/j.bjorl.2018.03.001. Epub 2018 Apr 7.
Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin.
The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin.
Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days. Cisplatin+gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days and a single intraperitoneal dose of 15mg/kg cisplatin at 3rd day. A control group received 1mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses.
In cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the cisplatin+gallic acid group, this biochemical, histopathological and functional changes were reversed.
In the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic emissions test results, biochemical findings and immunohistochemical analyses.
顺铂是一种广泛用于治疗多种癌症的抗肿瘤药物。耳毒性是限制顺铂使用的主要副作用之一。
本研究旨在从生化、功能和组织病理学角度探讨没食子酸对顺铂所致耳毒性的保护作用。
纳入28只雌性Sprague Dawley大鼠。将大鼠随机分为四组,每组7只。顺铂组腹腔注射单次剂量15mg/kg顺铂。没食子酸组连续5天腹腔注射100mg/kg没食子酸。顺铂+没食子酸组连续5天腹腔注射100mg/kg没食子酸,并在第3天腹腔注射单次剂量15mg/kg顺铂。对照组连续5天腹腔注射1mL生理盐水。给药前,所有大鼠均接受畸变产物耳声发射测试。在研究的第6天重复该测试。然后处死所有大鼠;取出耳蜗用于生化和组织病理学分析。
顺铂组第6天的信噪比显著低于其他组。此外,与对照组相比,耳蜗组织中的丙二醛水平显著升高,超氧化物歧化酶和谷胱甘肽过氧化物酶活性显著降低。组织病理学评估显示血管纹侵蚀,内皮细胞结缔组织层变性和水肿,外毛细胞损伤以及这些细胞数量减少。在顺铂+没食子酸组中,这些生化、组织病理学和功能变化得到逆转。
根据我们的研究结果,我们认为没食子酸可能对大鼠顺铂诱导的耳毒性起到了保护作用,畸变产物耳声发射测试结果、生化结果和免疫组织化学分析表明了这一点。