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Mechanisms Involved In Ototoxicity

机译：涉及耳毒性的机制

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The modern era or evidence-based ototoxicity emerged in the 1940s following the discovery of aminoglycosides and their ototoxic side effects. New classes of ototoxins have been identified in subsequent decades, notably loop diuretics, antineoplastic drugs, and metal chela-tors. Ototoxic drugs are frequently nephrotoxic, as both organs regulate fluid and ion composition. The mechanisms of ototoxicity are as diverse as the pharmacological properties of each ototoxm, though the generation of toxic levels of reactive oxygen species appears to be a common denominator. As mechanisms of cytotoxicity for each ototoxm continue to be elucidated, a new frontier in ototoxicity is emerging: How do ototoxins cross the blood-labyrinth barrier that tightly regulates the composition of the inner ear fluids? Increased knowledge of the mechanisms by which systemic ototoxins are trafficked across the blood-labyrinth barrier into the inner ear is critical to developing new pharmacotherapeutic agents that target the blood-labyrinth barrier to prevent trafficking of ototoxic drugs and their cytotoxic sequelae.
机译：在发现氨基糖苷及其耳毒性副作用后，现代时代或循证耳毒性出现在1940年代。在随后的几十年中，已经发现了新的一类毒素，特别是loop利尿剂，抗肿瘤药和金属螯合剂。耳毒性药物经常具有肾毒性，因为这两个器官都可调节体液和离子成分。耳毒性的机理与每种耳毒性的药理特性一样多样，尽管活性氧的毒性水平的产生似乎是一个共同点。随着每种毒素的细胞毒性机理的研究不断阐明，耳毒性的新领域正在出现：毒素如何穿越严格控制内耳液成分的血液迷宫屏障？对全身性毒素通过血液迷宫屏障转运到内耳的机制的了解增加，对于开发针对血液迷宫屏障的新药物治疗剂至关重要，以防止耳毒性药物及其细胞毒性后遗症的运输。

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