Potential Therapeutic Agents

ABSTRACT

Acquired hearing loss, which can develop after noise insult or ototoxic drug treatment, is a significant clinical, social, and economic issue. A major advance in our understanding came with the discovery that intense metabolic activity in the inner ear drives the formation of free radicals (short-lived, unstable, highly reactive clusters of atoms) in multiple types of cells in the inner ear after both noise and drug insult. Animal studies have now shown that free radicals formed during and after metabolic stress importantly contribute to acquired hearing loss. These new mechanistic insights provided for the first time a rationale for directly treating the inner ear to prevent hearing impairment. Consequently, use of free radical scavengers, or antioxidants, to prevent acquired hearing loss became a clinically relevant research goal. Many laboratories have now demonstrated that a variety of free radical scavengers reduce the potential for acquired hearing loss in animal subjects. Scientific data, supporting the use of these agents to prevent environmentally acquired hearing loss, is reviewed. Translational investigations are now essential to confirm the potential utility of these agents in the human inner ear. This article reviews the pharmacological otoprotective agents in or approaching clinical trials to prevent noise-, aminoglycoside-, and cisplatin-induced hearing loss.

KEYWORDS

Noise-induced hearing loss - ototoxicity - otoprotection - D-methionine - N-acetylcysteine - ebselen - amifostine - sodium thiosulfate - aspirin - β-carotene - vitamin C - vitamin E - magnesium

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