Güneri Enis Alpin, Olgun Yüksel, Aslıer Mustafa, Nuti Daniele, Kırkım Günay, Mungan Serpil, Kolatan Efsun, Aktaş Safiye, Trabalzini Franco, Ellidokuz Hülya, Yılmaz Osman, Mandala Marco
Department of Otorhinolaryngology, Dokuz Eylül University School of Medicine, İzmir, Turkey.
J Int Adv Otol. 2017 Apr;13(1):47-52. doi: 10.5152/iao.2016.2181. Epub 2017 Jan 13.
The aim of this study is to evaluate the effects of an intratympanic gentamicin-dexamethasone combination on the inner ear.
Twenty-six Wistar albino rats were divided into four groups: Group I (Control), group II (Intratympanic dexamethasone; ITD), group III (Intratympanic gentamicin; ITG), and group IV (Intratympanic gentamicin and dexamethasone; ITGD). On the first day after basal auditory brainstem response (ABR) measurements, the ITG group received 0.03 mL of intratympanic gentamicin (26.7 mg/mL). Intratympanic injection of 0.06 mL of a solution containing 13.35 mg/mL gentamicin and 2 mg/mL dexamethasone was performed in the ITGD group. 0.03 mL of physiological intratympanic serum and dexamethasone (4 mg/mL) was applied in control and ITD groups, respectively. On the 7th day, ABR measurements were repeated and vestibular functions were evaluated. On the 21th day, ABR and vestibular tests were repeated, and the animals were sacrificed for histopathological investigation.
The ITG group's hearing thresholds deteriorated in all frequencies. The ITGD group's hearing thresholds were significantly better than the ITG group, except at 8 kHz on the 7th day and in all frequencies at the 21th day measurements. The vestibular function scores of the ITG and ITGD groups were higher than the controls. Apoptotic changes were seen in cochlea, spiral ganglion, and vestibule of the ITG group. Cochlear and vestibular structures were well preserved in the ITGD group, similar to the controls.
The ITGD combination led to a significant hearing preservation. Although in subjective vestibular tests, it seemed that vestibulotoxicity was present in both ITG and ITGD groups the histopathological investigations revealed no signs of vestibulotoxicity in the ITGD group in contrast to the ITG group. Further studies using a combination of different concentrations of gentamicin and dexamethasone are needed.
本研究旨在评估鼓室内庆大霉素-地塞米松联合用药对内耳的影响。
将26只Wistar白化大鼠分为四组:第一组(对照组)、第二组(鼓室内注射地塞米松;ITD)、第三组(鼓室内注射庆大霉素;ITG)和第四组(鼓室内注射庆大霉素和地塞米松;ITGD)。在进行基础听性脑干反应(ABR)测量后的第一天,ITG组接受0.03 mL鼓室内注射庆大霉素(26.7 mg/mL)。ITGD组鼓室内注射0.06 mL含13.35 mg/mL庆大霉素和2 mg/mL地塞米松的溶液。对照组和ITD组分别鼓室内注射0.03 mL生理血清和地塞米松(4 mg/mL)。在第7天,重复进行ABR测量并评估前庭功能。在第21天,再次进行ABR和前庭测试,并对动物进行处死以进行组织病理学检查。
ITG组所有频率的听力阈值均恶化。ITGD组的听力阈值明显优于ITG组,但在第7天8 kHz时以及第21天所有频率测量时除外。ITG组和ITGD组的前庭功能评分高于对照组。ITG组的耳蜗、螺旋神经节和前庭出现凋亡变化。与对照组相似,ITGD组的耳蜗和前庭结构保存良好。
ITGD联合用药可显著保护听力。虽然在主观前庭测试中,ITG组和ITGD组似乎都存在前庭毒性,但组织病理学检查显示,与ITG组相比,ITGD组没有前庭毒性迹象。需要进一步研究使用不同浓度庆大霉素和地塞米松的联合用药。