Free radicals and hearing. Cause, consequence, and criteria.

Reactive oxygen and nitrogen species, including free radicals, are produced in the human body in both health and disease. In health, they may arise as regulatory mechanisms, intercellular signaling species, or as bacteriocidal agents. Their production is normally controlled by the antioxidant defense mechanisms that include intracellular enzymes--for example, glutathione peroxidase and superoxide dismutase--and low molecular-mass compounds such as vitamin E or ascorbic acid. Although repair mechanisms exist, some steady-state basal oxidative damage occurs in all individuals. Oxidative stress arises when there is a marked imbalance between the production and removal of reactive oxygen and nitrogen species. This may originate from an overproduction of these substances or from a depletion in the antioxidant defenses. Certain drugs may induce oxidative stress by forming drug-derived radicals that can not only deplete the antioxidant defenses but can also react directly with biomolecules. To be able to assess whether oxidative stress is occurring in a particular tissue, reliable biomarkers of oxidative damage are required. Since oxidative stress can damage all major biomolecules in vitro and probably in vivo, biomarkers for DNA, protein, and lipid damage are being developed which, when taken with an assessment of the antioxidant status of the individual, will allow evaluation of the involvement of oxidative stress in the etiology of disease and in the side effects of drugs. There is some evidence to suggest that free radical-mediated damage may be involved in the ototoxicity of aminoglycosides and cisplatin derivatives. Whether this is a cause or consequence of the toxic insult to the sensory hair cells of the inner ear remains to be determined.