Dose-dependent effects of D-methionine for rescuing noise-induced permanent threshold shift in guinea-pigs.
The purpose of this study was to examine the dose-response effectiveness of d-methionine (d-met) in rescuing a noise-induced permanent threshold shift (PTS) and cochlear biochemistry following noise exposure. One hour after being exposed to continuous broadband white noise at 105dB sound pressure level (SPL) for 6h, guinea-pigs were treated five times at 12-h intervals with 200, 400, or 600mg/kg d-met or sterile 0.9% saline (each group, N=6) by intraperitoneal injection. Six guinea-pigs with normal hearing that were not exposed to noise served as control animals. Although administration of d-met 200mg/kg did not significantly reduce the mean PTS, treatment with d-met 600mg/kg achieved a complete rescue response. The level of rescue from noise-induced PTS following treatment with 200, 400, or 600mg/kg d-met was dose dependent. The attenuation of the noise-induced decreases in the activities of the Na(+), K(+)-ATPase and Ca(2+)-ATPase following treatment with 200, 400, or 600mg/kg d-met was also dose dependent. Likewise, d-met-dose-dependent decreases in mean lipid peroxidation and nitric oxide levels were observed in the d-met treated groups. Significant attenuation of increased oxidative stress and decreased ATPase activities was concurrent with the d-met-mediated improvements in noise-induced auditory dysfunction.
Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan; Oriental Institute of Technology, Taipei, Taiwan; Department and Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
W-C
WC
Lo
L-J
LJ
Liao
C-T
CT
Wang
Y-H
YH
Young
Y-L
YL
Chang
P-W
PW
Cheng
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects* / Q000502:physiology*; D006168:Guinea Pigs; D008715:Methionine / Q000494:pharmacology*; D009622:Noise / Q000009:adverse effects*; D011897:Random Allocation
D008715:Methionine
ABR; ALCAR; ATPase; EP; GSH; GSSG; LPO; MDA; NIHL; NO; PTS; RNS; ROS; SPL; TTS; acetyl-l-carnitine; auditory brainstem response; d-methionine; endocochlear potential; glutathione; lipid peroxidation; malondialdehyde; nitric oxide; noise-induced hearing loss; oxidized glutathione; permanent threshold shift; reactive nitrogen species; reactive oxygen species; sound pressure level; temporary threshold shift