Anti-oxidation Capability and Environmental Factors for Noise Induced Hearing Loss

• Main Authors: Cheng-YuLin, 林政佑
• Other Authors: Perng-Jy Tsai
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/69406255997328056690

博士 === 國立成功大學 === 環境醫學研究所 === 98 === Noise-induced hearing loss (NIHL) is a complex disease which might be caused by interactions between environmental and genetic factors. Noise is the best-known and one of the most studied environmental factors causing hearing loss. Genetic factors may modify the susceptibility to noise. The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying NIHL. Glutathione is an important cellular antioxidant that limits cell damage by ROS. This is a three-part study. The first part was a cross-sectional study. It was to create a reference database that can be used for epidemiological studies of hearing impairment (as determined by otological status assessment and standardized audiological tests) in the Taiwanese population. A systematic stratified sampling framework involving the seven administrative areas in Tainan City was used, with each family being the basic sampling unit. All family members ＞20 years old, who consented to undergo all the examinations, were included. The overall prevalence of hearing impairment (＞25 dB) in the population in Taiwan was 21.4%. Middle ear disease was a significant risk factor for hearing impairment in addition to age and gender. The prevalence of occupational noise exposure for female subjects was 4.4%, and that for male subjects was 18.3%. Therefore, NIHL is an important issue for further research. In the second part, we investigated whether Glutathione S-transferase (GST) genetic variants in the human antioxidant system were associated with the susceptibility to NIHL. The noise-exposed workers from steel industries in Southern Taiwan, who have worked for more than 5 years, were recruited. Firstly, questionnaires interview about noise exposure, smoking, alcohol drinking, drug habit history and calculation of Body Mass Index (BMI) were done. After detailed local examination with otoscope, these subjects received hearing tests by pure-tone audiometry (PTA) before and after their daily works. The amount of noise exposure was calculated by Job-Exposure Matrix (JEM) using average yearly site-specific noise monitoring data and individual workers’ job history, to yield life-time total noise exposure level. Blood samples were collected. Deletion polymorphisms in the GSTT1 and GSTM1 genes, and single nucleotide polymorphisms (SNPs) in GSTP1 were determined. Statistical analysis was performed to compare their respective genotype frequencies. We found that noise-induced temporary threshold shift (TTS) for high frequencies (HF) by PTA was related to the daily noise exposure. It suggested that pre-shift hearing impairment and daily noise exposure had impacts on TTS for HF by PTA. Based on combinatory analysis, we found that individuals carrying all genotypes with GSTM1 null, GSTT1 null, and GSTP1 Ile105/Ile105 were more susceptible to noise-induced TTS. In addition, the JEM model-based estimates provided a significant dose-response relationship between noise exposure and noise-induced permanent threshold shift (PTS). We found that workers carrying GSTM1 null, GSTT1 null and GSTP1 Ile105/Ile105 genotypes were susceptible to noise-induced PTS, when a corresponding 40-year noise exposure level was higher than 90 dBA. In the third part of the study, we conducted a study to determine whether the antioxidant, N-Acetylcysteine (NAC), protected men against noise-induced TTS, and whether subgroups with genetic polymorphisms of GSTM1 and GSTT1 responded to NAC differently. Our results presented that NAC significantly reduced noise-induced TTS. When the participants were grouped by GST M1/T1 genotypes, the NAC effect was only significant among workers with null genotypes in both GSTM1 and GSTT1. In conclusion, the results of this study might help elucidate the relative importance of antioxidant enzymes as risk factors for NIHL. We also proved that the use of NAC could significantly reduce noise-induced TTS. Further studies should include a greater number of participants and involve workers exposed to different patterns of noise (i.e., steady noise, fluctuating noise, and impulse noise). Moreover, investigations of other genotypic variants involved in oxidative stress response for elucidating the gene-environment interaction for NIHL are warranted. We would also like to examine whether noise-induced PTS could be significantly reduced by the prophylactic oral administration of NAC in a prospective, randomized double-blind cross-over trial.