L&L Therapy Services, LLC

Within the next decade audiologists will be working with patients and physicians in selecting and monitoring pharmacologic otoprotective agents against drug and noise induced hearing loss either for research or clinic applications or both. Currently, several of these agents are in clinical trials, although none yet have Food and Drug Administration approval for clinical use.

Cisplatin is a potent chemotherapy drug that is still used frequently in spite of its many toxic side effects, of which ototoxicity is among the most severe. Modern research has provided new insights into the biological mechanisms of cisplatin-induced cochlear damage and has opened new avenues for co-treatments to potentially reduce or eliminate the ototoxicity. As has proven to be the case with noise-induced hearing loss and age-related hearing loss, oxidative stress has a key role in cisplatin ototoxicity. Additionally, like with noise and aging, apoptotic cell death has been identified as the primary mode of cell death in cochleae exposed to cisplatin. The current review begins with a description of cisplatin ototoxicity and its mechanisms. Interventions that target a reduction of oxidative stress or intercession in the apoptotic cell death pathway as a means of limiting cisplatin-induced hearing loss are then discussed in the second half of the review.

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. Although we once thought virtually all NIHL was a consequence of mechanical damage to cells in the inner ear, we now know that intense metabolic activity drives the formation of free radicals (short-lived, unstable, highly reactive clusters of atoms) in the inner ear. Studies in animals clearly have shown that free radicals formed during and after noise contribute importantly to NIHL, and many laboratories have demonstrated that free radical scavengers ("antioxidants") reduce NIHL in animal subjects. Our group, including investigators at multiple institutions, specifically has shown the combination of beta-carotene, vitamins C and E, and magnesium is highly effective in preventing NIHL and sensory cell death in guinea pigs and mice. Others have shown benefit in animal models with agents such as N-acytelcysteine, D-methionine, and ebselen. Use of free radical scavengers or antioxidants to prevent noise-induced deficits thus has become a clinical research goal. Given the multitude of intracellular events that occur during and after noise, it is possible that combinations of agents will ultimately prove to be a useful therapeutic approach. Translational investigations are essential to confirm potential utility of these agents in the human inner ear.