Yüksel Aslıer Nesibe Gül, Tağaç Aylin Altınışık, Durankaya Serpil Mungan, Çalışır Meryem, Ersoy Nevin, Kırkım Günay, Yurdakoç Kadir, Bağrıyanık Hüsnü Alper, Yılmaz Osman, Sütay Semih, Güneri Enis Alpin
Dokuz Eylül University, School of Medicine, Department of Otorhinolaryngology, Izmir, Turkey.
Dokuz Eylül University, Faculty of Arts and Sciences, Department of Chemistry, Izmir, Turkey.
Int J Pediatr Otorhinolaryngol. 2019 Jul;122:60-69. doi: 10.1016/j.ijporl.2019.04.003. Epub 2019 Apr 3.
The aim of this study was to investigate the protective effects of a sustained release form of dexamethasone (dex) loaded chitosan-based genipin-cross-linked hydrogel (CBGCH) in a guinea pig model of cisplatin (CP) induced hearing loss.
Implantation of CBGCH was made by intratympanic (IT) injection. Ototoxicity was produced by intraperitoneal (IP) single dose of 14 mg/kg CP. Animals were randomly divided into four groups with 6 guinea pigs in each. Group 1 received only IP CP; group 2 received only IT dex-loaded CBGCH injections. Group 3 and group 4 received IP CP, plus IT nondrug CBGCH and IT dex-loaded CBGCH respectively 24 h prior to IP CP injections. Distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were obtained before the treatments and solely ABR measurements were done after 3 and 10 days. The ultrastructural effects were investigated by scanning electron microscopy (SEM) analysis.
The postCP ABR thresholds at 4, 8, 12, 16, 32 kHz frequencies were significantly better in group 4 than groups 1 and 3 (p < 0.05). The comparison of time effective ABR thresholds between groups 1 and 4 and between groups 3 and 4 showed significantly lower ABR thresholds in group 4 (p < 0.05). The SEM analysis showed that stereocilia of inner and outer hair cells were preserved in group 4, almost like group 2, whereas cytotoxic degenerations were noted in groups 1 and 3.
Intratympanic administration of dex-loaded CBGCH has been shown to provide functional and structural protection against CP-induced ototoxicity.
本研究旨在探讨地塞米松（dex）负载的壳聚糖基京尼平交联水凝胶（CBGCH）缓释剂型对顺铂（CP）诱导的豚鼠听力损失模型的保护作用。
通过鼓室内（IT）注射植入CBGCH。通过腹腔内（IP）单剂量14mg/kg CP产生耳毒性。将动物随机分为四组，每组6只豚鼠。第1组仅接受IP CP；第2组仅接受IT载dex的CBGCH注射。第3组和第4组在IP CP注射前24小时分别接受IP CP，外加IT非药物CBGCH和IT载dex的CBGCH。在治疗前获得畸变产物耳声发射（DPOAE）和听性脑干反应（ABR）测量值，仅在3天和10天后进行ABR测量。通过扫描电子显微镜（SEM）分析研究超微结构效应。
第4组在4、8、12、16、32kHz频率下的CP后ABR阈值明显优于第1组和第3组（p<0.05）。第1组和第4组之间以及第3组和第4组之间的时间有效ABR阈值比较显示，第4组的ABR阈值明显更低（p<0.05）。SEM分析表明，第4组内、外毛细胞的静纤毛得以保留，几乎与第2组一样，而第1组和第3组则出现了细胞毒性退变。
鼓室内给予载dex的CBGCH已被证明可提供针对CP诱导的耳毒性的功能和结构保护。
