Semin Hear 2003; 24(2): 123-134
DOI: 10.1055/s-2003-39839
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Oxidative Cochlear Injury and the Limitations of Antioxidant Therapy

Kevin K. Ohlemiller
  • Fay and Carl Simons Center for the Biology of Hearing and Deafness, Central Institute for the Deaf, St. Louis, Missouri
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Publikationsdatum:
11. Juni 2003 (online)

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ABSTRACT

Evidence has been amassed over the last 15 years implicating reactive oxygen species (ROS) in cochlear injury due to ischemia, noise, and ototoxicants. Because ROS appear to be broadly involved in most cellular injury processes, it might be expected that antioxidants applied with optimal timing, dose, and route should completely prevent cochlear injury. This expectation has remained unmet, however. Recent experiments involving noise injury in knockout mice for key antioxidant enzymes also have yielded surprisingly modest, even paradoxical, results. Research in the area of oxidative stress and deafness is moving into a more mature phase, wherein simplistic models and hypotheses are being modified to include more of the emerging complexity of reduction-oxidation (redox) biochemistry. Sensory cell injury and death probably includes parallel ROS-dependent and ROS-independent pathways. In addition, ROS-related processes are complex and include myriad checks and balances, such that the manipulation of a single component can produce unexpected results. Varied cochlear cell types and epithelia may differ in antioxidant capacity or sustain injury through different ROS-mediated cascades. Finally, some ROS serve as messengers, both under normal circumstances and as cells strive to maintain homeostasis after stress. Antioxidant therapy in some form nevertheless retains promise for protecting the cochlea from acute and chronic stress. Consideration of ROS within an appropriately broad cell biological context may favor combined pharmacological remedies.

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