Role of Free Radicals, Glutamate Toxicity, Glutathione Depletion in Apoptosis of Cochlear Hair Cells, Neuronal Cells among Patients with Sensorineural Hearing Loss

Vithal D. Udagatti, Rajendran Dinesh Kumar, A. Samorekar, Vaibhavi Kr
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Abstract

Abstract Introduction Hearing loss may lead to depression, decreased quality of life, reduced functional status and social isolation. The glutathione-S transferase (GSTS) is an antioxidant scavenging enzyme. Decreased glutathione and GSTS activity levels lead to an increase in susceptibility of hair-cell damage leading to sensorineural hearing loss. The cumulative effect of oxidative stress and mitochondrial damage by free radicals results in the mutation/deletion of deoxyribonucleic acid, leading to decline in mitochondrial function, which in turn plays an important role in inducing apoptosis of the cochlear cells. Other risk factors also include noise exposure, genetic predisposition, health comorbidities, ototoxic drugs, infections, and immune-mediated inflammation of auditory cells. Study Design Prospective, non-comparative, metacentric clinical study. Materials and Methods The study was carried out in 30 patients from 6/5/2016 to 10/1/2018. Total of 30 patients of sensorineural hearing loss were enrolled (17 males, 13 females). Clinical history, ENT examination, and audiogram were done, treatment duration of 8 weeks for each patient and followed up to 3 outpatient visits. The patient was administered rebamipide 100 mg, alpha lipoic acid 100 mg, and acetylcysteine 100 mg capsules twice a day for a total period of 8 weeks. Wherever giddiness was an added symptom, Cinnarizine 20mg with Diaminehydrate 40 mg combination twice a day was added up to complete relief of symptoms, thereafter once a day as maintenance dose over a period of 8 weeks. Wherever tinnitus was an added symptom, deflazacort 6 mg twice a day was added and tapered up to 1 month. If the symptom of tinnitus persisted, intratympanic steroid injection was given. During every visit, clinical assessment and audiogram were repeated. Results Our study demonstrated greater improvement in hearing at higher frequencies with 8 weeks of rebamipide 100 mg + alpha lipoic acid 100 mg + acetylcysteine 100 mg administration in 30 patients with twice-daily dosing. Conclusion Synthesis of free radicals in the inner ear may play an important part in the pathogenesis of sensory hearing loss. The combination of rebamipide 100 mg + alpha lipoic acid 100 mg + acetylcysteine 100 mg is effective prophylaxis in sensorineural hearing loss that addresses both factors of inhibiting the cochlear cell damage and enhancing cochlear cell preservation.
自由基、谷氨酸毒性、谷胱甘肽耗竭在感音神经性听力损失患者耳蜗毛细胞、神经元细胞凋亡中的作用
听力损失可能导致抑郁、生活质量下降、功能状态下降和社会孤立。谷胱甘肽s转移酶(GSTS)是一种抗氧化清除酶。谷胱甘肽和GSTS活性水平的降低导致毛细胞损伤的易感性增加,从而导致感音神经性听力损失。氧化应激和自由基对线粒体损伤的累积作用导致脱氧核糖核酸突变/缺失,导致线粒体功能下降,进而在诱导耳蜗细胞凋亡中起重要作用。其他风险因素还包括噪音暴露、遗传易感性、健康合并症、耳毒性药物、感染和免疫介导的听觉细胞炎症。研究设计前瞻性、非比较性、稳中心临床研究。材料与方法本研究于2016年6月5日至2018年10月1日对30例患者进行研究。共纳入30例感音神经性听力损失患者(男性17例,女性13例)。完成临床病史、耳鼻喉科检查、听力学检查,治疗时间8周,门诊随访3次。患者给予利巴米胺100 mg、α硫辛酸100 mg、乙酰半胱氨酸100 mg胶囊,每日2次,共8周。若伴有头晕症状,可将Cinnarizine 20mg与Diaminehydrate 40mg联合用药,每日2次,直至完全缓解症状,此后每日1次作为维持剂量,持续8周。如果耳鸣是一种附加症状,则添加地拉法克6毫克,每天两次,并逐渐减少至1个月。如耳鸣症状持续,给予鼓室内类固醇注射。每次就诊均进行临床评估和听力图检查。结果:我们的研究表明,30例患者每日两次给予雷巴米胺100 mg + α硫辛酸100 mg +乙酰半胱氨酸100 mg给药8周后,在更高频率下听力有更大的改善。结论内耳自由基的合成可能在感觉性听力损失的发病机制中起重要作用。利巴米胺100 mg + α硫辛酸100 mg +乙酰半胱氨酸100 mg联合应用可有效预防感音神经性听力损失,同时兼顾抑制耳蜗细胞损伤和增强耳蜗细胞保存的作用。
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