Cochlear detoxi fi cation: Role of alpha class glutathione transferases in protection against oxidative lipid damage, ototoxicity, and cochlear aging

Age-related hearing loss (AHL) is the most common form of hearing impairment. AHL is thought to be a multifactorial condition resulting from the interaction of numerous causes including aging, genetics, exposure to noise, and exposure to endogenous and exogenous toxins. Cells possess many detoxification enzymes capable of removing thousands of cytotoxic xenobiotics and endogenous toxins such as 4hydroxynonenal (4-HNE), one of the most abundant cytotoxic end products of lipid peroxidation. The cellular detoxification system involves three phases of enzymatic detoxification. Of these, the glutathione transferase (GST) detoxification system converts a toxic compound into a less toxic form by conjugating the toxic compound to reduced glutathione by GST enzymes. In this review, we describe the current understanding of the cochlear detoxification system and examine the growing link between GST detoxification, oxidative lipid damage, ototoxicity, and cochlear aging with a particular focus on the alpha-class GSTs (GSTAs). We also describe how exposure to ototoxic drugs, exposure to noise, or aging results in increased 4-HNE levels, how 4-HNE damages various cell components under stress conditions, and how GSTAs detoxify 4-HNE in the auditory system. (c) 2020 Elsevier B.V. All rights reserved.

Automated summary

Age-related hearing loss (AHL) is a multifactorial condition resulting from the interaction of aging, genetics, exposure to noise, and exposure to endogenous and exogenous toxins. The cellular detoxification system involves GST enzymes converting toxic compounds into less toxic forms, with GSTA playing a key role in the auditory system.