ROLE OF GLUTATHIONE IN PROTECTION AGAINST NOISE-INDUCED HEARING-LOSS

A potential mechanism of hearing loss due to acoustic overstimulation is the generation of reactive oxygen species (ROS). ROS not removed by antioxidant defenses could be expected to cause significant damage to the sensory cells of the cochlea. We studied the influence of the ant ioxidant glutathione (GSH) on noise-induced hearing loss by using L-bu thionine-[S,R]-sulfoximine (BSO), an inhibitor of GSH synthesis, and 2 -oxothiazolidine-4-carboxylate (OTC), a cysteine prodrug, which promot es rapid restoration of GSH when GSH is acutely depleted. Pigmented fe male guinea pigs were exposed to broadband noise (102 dB SPL, 3 h/day, 5 days) while receiving daily injections of BSO, OTC, or saline. By w eeks 2 and 3 after noise exposure, BSO-treated animals showed signific antly greater threshold shifts above 12 kHz than saline-treated subjec ts, whereas OTC-treated animals showed significantly smaller threshold shifts at 12 kHz than controls. Histologically assessed noise-induced damage to the organ of Corti, predominantly basal turn row 1 outer ha ir cells, was most pronounced in BSO-treated animals. High performance liquid chromatographic analysis showed that OTC significantly increas ed cysteine levels, but not GSH levels, in the cochlea. These findings show that GSH inhibition increases the susceptibility of the cochlea to noise-induced damage and that replenishing GSH, presumably by enhan cing availability of cysteine, attenuates noise-induced cochlear damag e. (C) 1998 Elsevier Science B.V.