Protection from Noise-Induced Temporary Threshold Shift by d-Methionine is Associated with Preservation of ATPase Activities

Abstract

The present study was designed to test whether noise-induced temporary threshold shift (TTS) could be attenuated by D-methionine and its possible relation to the biochemical changes of cochlear lateral walls such as ATPase activities and oxidative stress in guinea pigs. Thirty-two normal-hearing male guinea pigs were randomly divided into saline-treated and D-methionine-treated (300 mg/kg) experimental groups. One hour after treatment, they were exposed to a continuous broadband white noise at 105 +/- 2 dB sound pressure level for 10 min, causing TTS. Each group was then divided into four subgroups based on the number of survival days after noise exposure (0, 1, 2, and 7 days). Each subgroup had four animals and eight ears included. By means of click-evoked auditory brain stem responses (ABR), auditory thresholds of guinea pigs were measured before noise exposure, immediately after noise exposure, and before killing. After animals were killed, cochlear lateral walls were immediately harvested and assayed for enzyme-specific activities of Na+, K+-ATPase and Ca2+-ATPase, lipid peroxidation, and nitric oxide. A 15.31 +/- 3.80 dB threshold shift was found immediately after noise exposure in saline-pretreated guinea pigs. In contrast, ABR threshold shift was significantly attenuated to 4.06 +/- 2.35 dB in D-methionine-treated animals. Furthermore, D-methionine enhanced the restoration of ABR threshold to baseline level by 1 day. In addition, noise significantly decreased Na+, K+-ATPase, and Ca2+-ATPase activities and increased lipid peroxidation and nitric oxide levels of the cochlear lateral walls. D-methionine significantly protected against all of these changes. Noise not only induced TTS but also inhibited ATPase activities as well as increased oxidative stress in guinea-pig cochlear lateral walls; all of these changes could be attenuated by d-methionine through its antioxidative property. These results suggest the potential usefulness of d-methionine in protecting from noise-induced ototoxicity.