This research focuses on the relation between the cochlea's antioxidant system and resistance to noise or carboplatin. The project is a logical extension of previous research in our lab that showed (1) the ear could acquire resistance to noise by prior exposure to benign moderate level noise; (2) the antioxidant enzymes catalase, glutathione reductase and gamma-glutamyl cysteine synthtase (GCS) are increased in concentration in both stria and organ of Corti after prophylactic noise exposures; (3) the degree of temporary and permanent hearing loss as well as hair loss from exposures to a traumatic noise could be reduced by prior treatment of R- phenylisopropyladenoisine (R-PIA). Collectively, these results suggest that high level noise exposures produce hearing loss by the mechanism of reactive oxygen intermediates (ROI) cytotoxicity and that prophylactic noise exposures, as well as intervention by R-PIA, can reduce both the effects of noise and cisplatin (Ryback et al., 1995). The proposed set of experiments has four specific aims: (1) What is the relation between glutathione related enzymes (specifically GCS), and susceptibility to noise? (2) Can the susceptibility to noise-induced hearing loss be decreased with drugs that up-regulate GCS or increased with drugs that suppress GCS? (3) What is the normal anatomical distribution of glutathione (GSH) and does it change with exposure to noise? (4) Is the otoxicity of carboplatin influenced by drugs that up-regulate or down- regulate the antioxidant system? These experiments will be conducted on chinchillas. Hearing functions will be measured by evoked potentials and otoacoustic emissions. GCS levels will be assessed by our collaborator Dr. Howard Steinman at Albert Einstein College of Medicine. Cochlear analysis will include cell counts from surface preparations and confocal studies of GSH distribution.
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