Ototoxicity and noise trauma: electron transfer, reactive oxygen species, cell signaling, electrical effects, and protection by antioxidants: practical medical aspects.

Ototoxins are substances of various structures and classes. This review provides extensive evidence for involvement of electron transfer (ET), reactive oxygen species (ROS) and oxidative stress (OS) as a unifying theme. Successful application is made to the large majority of ototoxins, as well as noise trauma. We believe it is not coincidental that these toxins generally incorporate ET functionalities (quinone, metal complex, ArNO(2), or conjugated iminium) either per se or in metabolites, potentially giving rise to ROS by redox cycling. Some categories, e.g., peroxides and noise, appear to operate via non-ET routes in generating OS. These highly reactive entities can then inflict injury via OS upon various constituents of the ear apparatus. The theoretical framework is supported by the extensive literature on beneficial effects of antioxidants, both for toxins and noise. Involvement of cell signaling and electrical effects are discussed. This review is the first comprehensive one based on a unified mechanistic approach. Various practical medical aspects are also addressed. There is extensive documentation for beneficial effects of antioxidants whose use might be recommended clinically for prevention of ototoxicity and noise trauma. Recent research indicates that catalytic antioxidants may be more effective. In addition to ototoxicity, a widespread problem consists of ear infections by bacteria which are demonstrating increasing resistance to conventional therapies. A recent, novel approach to improved drugs involves use of agents which inhibit quorum sensors that play important roles in bacterial functioning. Prevention of ear injury by noise trauma is also discussed, along with ear therapeutics.