University of Utah, Adjunct Research Faculty, Division of Otolaryngology-Head and Neck Surgery, 50 N. Medical Drive, Salt Lake City, 84132, USA.
Expert Opin Drug Metab Toxicol. 2011 Dec;7(12):1521-34. doi: 10.1517/17425255.2011.614231. Epub 2011 Oct 14.
Drug ototoxicity represents one of the main preventable causes of deafness. Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, antimalarial medications, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and most recently described, acetaminophen when abused with narcotic medication. These medications are prescribed despite their side effects, which includes inner ear toxicity, because they are life-saving drugs or there is a lack of better treatment.
This review will discuss in vitro and in vivo models of ototoxicity highlighting recently published ototoxicity research. The reader will learn the strengths and limitations of different ototoxicity models and what molecular insights have been gained from their application. A better understanding of the cellular mechanisms of these ototoxins will help in the discovery of ways to prevent and treat hearing loss associated with ototoxic medications.
There are benefits to both in vitro and in vivo models of ototoxicity. Research of a particular medication and its ototoxic mechanisms should draw from several models, enabling a better answer to the clinical question of prevention and treatment of inner ear drug toxicity.
药物耳毒性是可预防的耳聋主要原因之一。氨基糖苷类和大环内酯类抗生素、抗疟药物、袢利尿剂、铂类化疗药物、一些非甾体抗炎药以及最近描述的、与麻醉药物滥用的对乙酰氨基酚都具有耳毒性。尽管这些药物有副作用,包括内耳毒性,但仍被开处,因为它们是救命药物,或者没有更好的治疗方法。
本综述将讨论耳毒性的体外和体内模型,重点介绍最近发表的耳毒性研究。读者将了解不同耳毒性模型的优缺点,以及从其应用中获得的分子见解。更好地了解这些耳毒素的细胞机制将有助于发现预防和治疗与耳毒性药物相关的听力损失的方法。
体外和体内耳毒性模型都有其优势。对特定药物及其耳毒性机制的研究应该借鉴几种模型,以便更好地回答关于预防和治疗内耳药物毒性的临床问题。