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ShareApr. 12, 1999 — BUFFALO, N.Y. -- Researchers in the University at Buffalo Center for Hearing and Deafness have shown for the first time that a compound called leupeptin may help protect against the noise-induced hearing loss caused by living in noisy industrialized societies.
Using an animal model, researchers found that treating the inner ear with leupeptin before exposure to high-level noise, comparable to a jet engine, reduced the loss of sensory hair cells by 60 percent. Hair cells convert sound waves into electrical impulses that are sent to the brain.
Leupeptin, however, did not protect against the damaging effects of the anti-cancer drug carboplatin that can cause deafness in treated patients.
Results of the study, lead by Richard J. Salvi, Ph.D., professor of communicative disorders and sciences in UB's College of Arts and Sciences and co-director of the center, appear in the current issue (Vol. 10, No. 4) of NeuroReport.
"The results are very exciting for two reasons," Salvi said. "First, they provide clues to the cellular events that lead to sensory-cell death in the inner ear. Second, they suggest a potential drug-therapy approach to protecting the ear against sound damage."
Salvi and his colleagues at UB and his collaborators, Alfred Stracher, Ph.D., and Abraham Shulman, Ph.D., both at the SUNY Health Science Center at Brooklyn, have been investigating ways to protect the auditory system from damage via noise and ototoxic drugs, common causes of deafness in Western societies.
This study was based on the knowledge that, in many cases, degeneration of nerve function is caused by a cascade of events, beginning with a trauma that induces an increase of calcium in nerve cells. Excess calcium, in turn, increases the level of enzymes called calpains, which promote the breakdown of proteins and other factors critical to nerve functioning.
"Drugs that inhibit the action of calpains -- leupeptin is one -- have been shown to decrease or prevent destruction of nerve functioning that results in neuromuscular atrophy in cases of trauma or genetic disorders," Stracher noted.
Salvi and colleagues set out to determine if leupeptin also could protect the sensory hair cells in the ear from noise and ototoxic drugs such as carboplatin -- knowing that such insults cause an increase in calpains -- and thus prevent hearing loss.
The researchers treated the right cochlea of chinchillas with leupeptin for 14 days. On the fifth day, some of the animals were exposed to noise, at 100 decibels or 105 decibels. The left ears of all animals served as controls. Results from the noise exposure study showed massive loss of hair cells in the ears not treated with leupeptin, while only a few hair cells were missing in the treated ear.
A similar study, designed to determine if leupeptin would protect against hair-cell loss caused by carboplatin, showed leupeptin offered no protection, Salvi said.
Additional researchers on the study were Jain Wang and Dalian Ding, research scientists in the UB Center for Hearing and Deafness.
The research was supported in part by the Martha Entenmann Tinnitus Research Foundation.
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