TY - JOUR
T1 - Role of glutathione in protection against noise-induced hearing loss
AU - Yamasoba, Tatsuya
AU - Nuttall, Alfred L.
AU - Harris, Craig
AU - Raphael, Yehoash
AU - Miller, Josef M.
N1 - Funding Information:
A preliminary report was presented at the 20th Midwinter Meeting of the Association for Research in Otolaryngology (February 2–6, 1997, at St. Petersburg Beach, FL). We thank Ms. J. Nadine Brown for her editorial help and Dr. John K.M. Coleman for his invaluable advice in statistical analysis. This work was supported by NIH grant DC00105.
PY - 1998/2/16
Y1 - 1998/2/16
N2 - 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 antioxidant glutathione (GSH) on noise-induced hearing loss by using L-buthionine-[S,R]- sulfoximine (BSO), an inhibitor of GSH synthesis, and 2-oxothiazolidine-4- carboxylate (OTC), a cysteine prodrug, which promotes rapid restoration of GSH when GSH is acutely depleted. Pigmented female 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 weeks 2 and 3 after noise exposure, BSO-treated animals showed significantly greater threshold shifts above 12 kHz than saline-treated subjects, 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 hair cells, was most pronounced in BSO- treated animals. High performance liquid chromatographic analysis showed that OTC significantly increased 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 enhancing availability of cysteine, attenuates noise-induced cochlear damage.
AB - 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 antioxidant glutathione (GSH) on noise-induced hearing loss by using L-buthionine-[S,R]- sulfoximine (BSO), an inhibitor of GSH synthesis, and 2-oxothiazolidine-4- carboxylate (OTC), a cysteine prodrug, which promotes rapid restoration of GSH when GSH is acutely depleted. Pigmented female 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 weeks 2 and 3 after noise exposure, BSO-treated animals showed significantly greater threshold shifts above 12 kHz than saline-treated subjects, 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 hair cells, was most pronounced in BSO- treated animals. High performance liquid chromatographic analysis showed that OTC significantly increased 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 enhancing availability of cysteine, attenuates noise-induced cochlear damage.
KW - Buthionine
KW - Cochlea
KW - Cysteine
KW - Glutathione
KW - Guinea pig
KW - Noise- induced hearing loss
KW - Oxothiazolidine carboxylate
KW - Reactive oxygen species
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U2 - 10.1016/S0006-8993(97)01156-6
DO - 10.1016/S0006-8993(97)01156-6
M3 - Article
C2 - 9518561
AN - SCOPUS:0032536419
SN - 0006-8993
VL - 784
SP - 82
EP - 90
JO - Brain research
JF - Brain research
IS - 1-2
ER -