Aminoglycoside-Induced Cochleotoxicity: A Review.
Aminoglycoside-Induced Cochleotoxicity: A Review.
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DOI：
10.3389/fncel.2017.00308
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发表时间：
2017
影响因子：
5.3
通讯作者：
Steyger PS
中科院分区：
文献类型：
--
作者：
Jiang M;Karasawa T;Steyger PS
氨基糖苷类抗生素被用于预防或紧急治疗许多危及生命的细菌感染，包括结核病、败血症、囊性纤维化的呼吸道感染、复杂的尿路感染和心内膜炎。虽然氨基糖苷类抗生素是临床上必不可少的抗生素，但经过70多年的研究，其对肾脏和内耳的选择性毒性的机制仍在不断地被揭开。氨基糖苷类药物全身给药后的毒性机制有：(1)跨内皮细胞和上皮屏障层的药物转运；(2)感觉细胞对这些药物的摄取；(3)细胞内生理通路的破坏。特定因素会增加药物中毒的风险，包括持续暴露在较高水平的环境声音中，以及选定的治疗剂，如环状利尿剂和糖肽。严重的细菌感染(需要救命的氨基糖苷治疗)会引起全身炎症反应，这也会加重耳毒性和永久性听力损失的程度。我们讨论了保护听觉和前庭功能免受氨基糖苷类耳毒性的前瞻性临床策略，包括减少耳蜗细胞或感觉细胞对氨基糖苷类药物的摄取，以及通过改善细胞内的细胞毒性来保护耳朵。
Aminoglycoside antibiotics are used as prophylaxis, or urgent treatment, for many life-threatening bacterial infections, including tuberculosis, sepsis, respiratory infections in cystic fibrosis, complex urinary tract infections and endocarditis. Although aminoglycosides are clinically-essential antibiotics, the mechanisms underlying their selective toxicity to the kidney and inner ear continue to be unraveled despite more than 70 years of investigation. The following mechanisms each contribute to aminoglycoside-induced toxicity after systemic administration: (1) drug trafficking across endothelial and epithelial barrier layers; (2) sensory cell uptake of these drugs; and (3) disruption of intracellular physiological pathways. Specific factors can increase the risk of drug-induced toxicity, including sustained exposure to higher levels of ambient sound, and selected therapeutic agents such as loop diuretics and glycopeptides. Serious bacterial infections (requiring life-saving aminoglycoside treatment) induce systemic inflammatory responses that also potentiate the degree of ototoxicity and permanent hearing loss. We discuss prospective clinical strategies to protect auditory and vestibular function from aminoglycoside ototoxicity, including reduced cochlear or sensory cell uptake of aminoglycosides, and otoprotection by ameliorating intracellular cytotoxicity.
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影响因子：
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