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 105 dB sound pressure level (SPL) for 6 h, guinea-pigs were treated five times at 12-h intervals with 200, 400, or 600 mg/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 200 mg/kg did not significantly reduce the mean PTS, treatment with D-met 600 mg/kg achieved a complete rescue response. The level of rescue from noise-induced PTS following treatment with 200, 400, or 600 mg/kg D-met was dose dependent. The attenuation of the noise-induced decreases in the activities of the Na+, K(+-)ATPase and Ca2+-ATPase following treatment with 200, 400, or 600 mg/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. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.