Bucak Abdulkadir, Ozdemir Cigdem, Ulu Sahin, Gonul Yucel, Aycicek Abdullah, Uysal Mukremin, Cangal Ahmet
Department of Otolaryngology, Afyon Kocatepe University, Faculty of Medicine, Afyonkarahisar, Turkey.
Laryngoscope. 2015 May;125(5):1175-82. doi: 10.1002/lary.25031. Epub 2015 Jan 13.
OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate the potential protective effect of curcumin on paclitaxel-induced ototoxicity in rats by means of immunohistochemical and histopathological analysis and distortion product otoacoustic emissions (DPOAEs).
Animal study.
Forty Sprague-Dawley rats were randomized into five groups. Group 1 was administered no paclitaxel and curcumin during the study. Groups 2, 3, 4 and 5 were administered 5 mg/kg paclitaxel; 200 mg/kg curcumin; 5 mg/kg paclitaxel, followed by 200 mg/kg curcumin; 200 mg/kg curcumin and a day later 5 mg/kg paclitaxel followed intraperitoneally by 200 mg/kg curcumin once a week for 4 consecutive weeks, respectively. After the final DPOAEs test, the animals were sacrificed and their cochlea were prepared for hematoxylin and eosin and caspase-3 staining.
The DPOAEs thresholds and histopathological and immunohistochemical findings were substantially correlated in all groups. The histopathologic findings in the cochlea of the paclitaxel-treated animals showed not only changes in the organ of Corti, but also damage to the stria vascularis and spiral limbus, including nuclear degeneration, cytoplasmic vacuolization, and atrophy of intermediate cells. Additionally, cochlear changes in group 2, such as intense apoptosis, were confirmed by caspase-3 immunohistochemical staining. In group 4, coreceiving curcumin could not sufficiently prevent paclitaxel-induced ototoxicity, and the results in group 5 were similar to the control group.
In our study, we have concluded that pre- and coreceiving curcumin can significantly protect the cochlear morphology and functions on paclitaxel-induced ototoxicity in rats. Curcumin might be considered as a potential natural product that, used as a dietary supplement, could be easily given to patients undergoing paclitaxel chemotherapy.
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目的/假设：本研究旨在通过免疫组织化学、组织病理学分析以及畸变产物耳声发射（DPOAE），研究姜黄素对紫杉醇诱导的大鼠耳毒性的潜在保护作用。
动物研究。
40只Sprague-Dawley大鼠随机分为五组。第1组在研究期间未给予紫杉醇和姜黄素。第2、3、4和5组分别给予5mg/kg紫杉醇；200mg/kg姜黄素；5mg/kg紫杉醇后给予200mg/kg姜黄素；200mg/kg姜黄素，一天后给予5mg/kg紫杉醇，随后每周腹腔注射200mg/kg姜黄素，连续4周。在最后一次DPOAE测试后，处死动物并制备其耳蜗用于苏木精-伊红染色和半胱天冬酶-3染色。
所有组的DPOAE阈值与组织病理学和免疫组织化学结果密切相关。紫杉醇处理动物的耳蜗组织病理学结果不仅显示柯蒂氏器的变化，还显示血管纹和螺旋缘受损，包括核变性、细胞质空泡化和中间细胞萎缩。此外，第2组耳蜗的变化，如强烈凋亡，通过半胱天冬酶-3免疫组织化学染色得到证实。在第4组中，联合使用姜黄素不能充分预防紫杉醇诱导的耳毒性，第5组的结果与对照组相似。
在我们的研究中，我们得出结论，预先给予和联合给予姜黄素可以显著保护大鼠耳蜗形态和功能免受紫杉醇诱导的耳毒性。姜黄素可能被认为是一种潜在的天然产物，作为膳食补充剂，可轻松给予接受紫杉醇化疗的患者。
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