PREVENTION OF SOLVENT AND NOISE-INDUCED HEARING LOSS
HENDERSON, DONALD Principal Investigator
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Toluene and styrene are two of the most commonly used solvents and both have been shown todamage the inner ear and cause a moderate, mid-frequency hearing loss. This proposal has fourbroad questions: (1) How do cells in the cochlea die with solvent intoxication? (2) Since solventsare neurotoxic as well as ototoxic, is there a central auditory change associated with solventexposure? (3) Do solvents interact with the effects of noise? (4) Are the effects of solvent (styreneand toluene) exposure prevented with antioxidant therapy? Our approach to study the ototoxicpotential of these chemicals is to use the Long-Evan rat as an experimental model, measure itshearing before and after solvent and noise exposure, examine the changes in the series of evokedpotentials from cochlea to cortex for evidence of neurotoxic changes, examine the sensory cells forevidence of cell death (necrosis or apoptosis) and oxidative stress. The first set of experimentsexplore the dose/response of each of the two chemicals. Subjects will be sacrificed at either 12 or24 hours after the exposure for evaluation of oxidative stress and mechanism of loss or 30 days toassess permanent hearing loss and pathology. The second experiment involves an assessment ofperipheral and CMS changes with solvent exposure. The third set of experiments explores theinteraction of noise and the chemicals. The subjects will be given a mild dose of the chemical (asdetermined in Experiment I) and then will be exposed for 12 hours to a 8 kHz octave band of noiseat a level that will cause a 10 to 30 dB PTS. The fourth experiment evaluates the effectiveness ofN-actylcysteine (L-NAC), trolox and carnitine (ALCAR), as a protective drugs for chemical and noiseinduced hearing loss. These studies will add to our knowledge by confirming the ototoxicity ofstyrene and toluene; it will clarify how the two solvents interact with noise; it will also clarify ifoxidative stress is a factor in solvent ototoxicity and finally, the study will explore the excitingpossibility that the ototoxic effects of solvents can be prevented with antioxidants.