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Friend or foe? Effect of oral resveratrol on cisplatin ototoxicity

机译:是敌是友?口服白藜芦醇对顺铂耳毒性的影响

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Objectives/Hypothesis Our objectives were to study effects of orally administered resveratrol (RV) against cisplatin (CDDP) ototoxicity in different doses and to investigate ultrastructural changes in the cochlea and brainstem. Study Design In vivo study using an animal model. Methods Thirty-two male Wistar albino rats were divided into six groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were made. In groups I, II, and III, only saline, RV, and CDDP were given, respectively. Group IV, V, and VI animals were administered 10 mg/kg/day, 1 mg/kg/day, and 0.1 mg/kg/day of RV for 10 days, respectively, before 16 mg/kg CDDP injections were administered on day 11. All animals were sacrificed after repeated DPOAEs and ABR measurements were made on day 14. Cochleas of animals were investigated with transmission electron microscopy. Apoptosis were investigated with caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in the brainstem. Results In groups IV and V, DPOAEs and ABR findings revealed that oral administration of RV 10 mg/kg/day and 1 mg/kg/day doses before CDDP injection enhanced ototoxicity. In group VI, electomicroscopy revealed better ultrastructural findings than in the cisplatin group; however, these changes were not reflected in the audiological findings accordingly. Conclusions Our results implied that there were noticeable differences between different oral RV doses used for cisplatin ototoxicity. Especially in higher doses, RV was observed to enhance cisplatin ototoxicity.
机译:目的/假设我们的目的是研究口服白藜芦醇(RV)对不同剂量的顺铂(CDDP)耳毒性的影响,并研究耳蜗和脑干的超微结构变化。研究设计使用动物模型进行的体内研究。方法将32只雄性Wistar白化病大鼠分为六组。进行基线失真产物耳声发射(DPOAE)和听性脑干反应(ABR)测量。在I,II和III组中,仅分别给予生理盐水,RV和CDDP。在每天注射16 mg / kg CDDP之前,分别对IV,V和VI组的动物分别给予10 mg / kg /天,1 mg / kg /天和0.1 mg / kg /天的RV,持续10天。 11.重复DPOAE后处死所有动物,并在第14天进行ABR测量。用透射电子显微镜研究动物的耳蜗。用caspase-3活性和末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记(TUNEL)方法研究了脑干的凋亡。结果在IV和V组中,DPOAEs和ABR结果表明,在CDDP注射前口服RV 10 mg / kg / day和1 mg / kg / day剂量可增强耳毒性。在第六组中,电镜检查显示出比顺铂组更好的超微结构发现。然而,这些变化并未相应地反映在听力学的发现中。结论我们的研究结果表明,口服顺铂的耳毒性不同,口服RV剂量之间存在明显差异。特别是在较高剂量下,观察到RV可增强顺铂耳毒性。

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