McGill Auditory Sciences Laboratory, McGill University, Montreal, Quebec, Canada.
Otolaryngol Head Neck Surg. 2011 Sep;145(3):452-7. doi: 10.1177/0194599811406673. Epub 2011 Apr 26.
To determine whether intratympanic administration of dexamethasone reduces ototoxicity from systemic cisplatin.
Prospective animal study. Setting. Cisplatin chemotherapy induces ototoxicity manifesting as irreversible, sensorineural hearing loss. This is due to damage to the inner ear structures by free radicals. Steroidal anti-inflammatories have been shown to reduce the formation of free radicals and protect hearing in animal models.
Pure tone auditory brainstem responses were obtained in 58 female albino guinea pigs before and 3 days after intraperitoneal (IP) cisplatin chemotherapy. Auditory brainstem responses were also taken up to 1 month after a low dose of cisplatin. Part I consisted of a dosing study to determine the optimal ototoxic dose of cisplatin. In part II, auditory brainstem response thresholds were compared after bilateral intratympanic dexamethasone doses to act as controls. For part III, the otoprotection of dexamethasone against cisplatin was tested in separate bilateral and unilateral studies.
IP injection of 12 mg/kg of cisplatin induced significant hearing loss (57.2 ± 4.4 dB, P < .01) with 0% mortality. Ears treated with intratympanic dexamethasone alone showed no significant threshold changes. Ears that received IP cisplatin and intratympanic dexamethasone showed reduced threshold shifts at 8 kHz when the greatest concentration of dexamethasone was administered.
Modest intratympanic dexamethasone otoprotection of the guinea pig ear was greatest at the highest concentration tested and occurred in a frequency-dependent manner. Intratympanic dexamethasone presents as a safe, simple, and effective treatment modality to minimize cisplatin ototoxicity without interfering with the chemotherapeutic effects of cisplatin.
确定鼓室内给予地塞米松是否能降低全身顺铂引起的耳毒性。
前瞻性动物研究。背景：顺铂化疗可引起耳毒性，表现为不可逆的感音神经性听力损失。这是由于自由基对内耳结构的损伤所致。甾体类抗炎药已被证明可减少自由基的形成，并在动物模型中保护听力。
58 只雌性白化豚鼠在腹腔内（IP）顺铂化疗前和化疗后 3 天分别进行纯音听觉脑干反应测试。化疗后 1 个月内也进行了听觉脑干反应测试。第一部分是剂量研究，以确定顺铂的最佳耳毒性剂量。第二部分是双侧鼓室内给予地塞米松剂量作为对照，比较听觉脑干反应阈值。第三部分是在单独的双侧和单侧研究中测试地塞米松对顺铂的耳保护作用。
IP 注射 12 mg/kg 的顺铂可引起明显的听力损失（57.2±4.4 dB，P<.01），且无死亡率。单独鼓室内给予地塞米松治疗的耳朵无明显阈值变化。同时接受 IP 顺铂和鼓室内地塞米松治疗的耳朵在给予最大浓度地塞米松时，8 kHz 的阈值变化减小。
豚鼠耳的适度鼓室内地塞米松耳保护作用在测试的最高浓度时最大，且呈频率依赖性。鼓室内地塞米松是一种安全、简单、有效的治疗方法，可最大限度地减少顺铂耳毒性，而不干扰顺铂的化疗效果。
