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|Year : 2014
: 16 | Issue : 71 | Page
|Comparison of the effects of N-acetyl-cysteine and ginseng in prevention of noise induced hearing loss in male textile workers
Afsaneh Doosti1, Yones Lotfi1, Abdollah Moossavi1, Enayatollah Bakhshi2, Azita Hajhossein Talasaz3, Ahmad Hoorzad4
1 Department of Audiology, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
2 Department of Biostatistics, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
3 Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Occupational Medicine, Institute of Salamat Gostar of Occupational Medicine, Tehran, Iran
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|Date of Web Publication||18-Jul-2014|
Previous studies revealed the role of antioxidant agents in prevention of noise induced hearing loss (NIHL). The aim of this study was to compare the protective effect of N-acetyl-cysteine (NAC) and ginseng on protection of NIHL in textile workers exposed to continuous noise in daily working. In this study, 48 participants were randomly allocated to three groups; Group I received NAC 1200 mg/day, Group II received ginseng 200 mg/day, and Group III (control group) received no supplement. Pure tone audiometry and high frequency audiometry were performed preshift before and after 14 days (on day 15). Linear regression analysis results showed reduced noise-induced temporary threshold shift (TTS) for NAC and ginseng groups at 4, 6 and 16 kHz (P < 0.001) in both ears. Furthermore, the protective effects were more prominent in NAC than ginseng. Our results show that NAC and ginseng can reduce noise induced TTS in workers exposed to occupational noise. Further studies are needed to prove antioxidants benefits in hearing conservation programs.
Keywords: Antioxidants, ginseng, N-acetyl-cysteine, noise induced hearing loss
|How to cite this article:|
Doosti A, Lotfi Y, Moossavi A, Bakhshi E, Talasaz AH, Hoorzad A. Comparison of the effects of N-acetyl-cysteine and ginseng in prevention of noise induced hearing loss in male textile workers. Noise Health 2014;16:223-7
|How to cite this URL:|
Doosti A, Lotfi Y, Moossavi A, Bakhshi E, Talasaz AH, Hoorzad A. Comparison of the effects of N-acetyl-cysteine and ginseng in prevention of noise induced hearing loss in male textile workers. Noise Health [serial online] 2014 [cited 2020 Sep 27];16:223-7. Available from: http://www.noiseandhealth.org/text.asp?2014/16/71/223/137057
| Introduction|| |
Noise induced hearing loss (NIHL) is one of the most prevalent occupational diseases and industrialization made it very common.  NIHL is important from the clinical, social and economical point.  According to the American Speech, Language and Hearing Association and the Occupational Safety and Health Association 10 million Americans suffer from irreversible NIHL and about 30 million are exposed to hazardous levels of noise. 
Previous studies showed that physical or mechanical mechanisms cause NIHL, , but recently, the role of metabolic mechanisms are also introduced. ,,,,,,, Recent studies have revealed that noise increases the oxidative stress. 
Loud noise lead to structural changes in hair cell membrane causing production of free radicals like reactive oxygen species (ROS),  which are very reactive due to an unpaired valence shell electrons. Accumulation of ROS causes failure in antioxidant's action in neutralizing free radicals; consequently inner hair cells (IHCs) and largely outer hair cells (OHCs) cellular lipids, proteins and DNA damage and cells die through either apoptosis (programmed cell death) or necrosis. ,, As antioxidants scavenge and remove ROS and the other free oxygen radicals, they can prevent cells from dangerous materials. Two ways exist to increase antioxidant levels: Endogenous way (using sound conditioning) and exogenous way (direct infusion into the cochlea or systematic infusion into the whole body). 
Some studies showed that antioxidants such as glutathione (GSH) and ginsenosides (found in ginseng) can prevent hair cells from damage and hearing loss. ,
N-acetyl-cysteine (NAC) is a GSH precursor, which deacetylates to cysteine in the liver or local tissue and can neutralize the effect of noise  and increases GSH production,  which is one of the important antioxidants in the body, and has a critical role in inaction of free radicals, especially ROS , in the organs influenced by oxidative stress or exogenous toxins.
Ginseng extracts have various pharmaceutical components such as ginsenosides, which have antioxidant (anti-ROS and anti-apoptotic) features and consequently play an important role in preventing NIHL. Major active ingredients of ginseng such as ginsenosides or saponin have anti-oxidative effects. ,
In this randomized clinical trial, we investigated the effect of NAC and ginseng (Panax ginseng CA Meyer or Korean red ginseng [KRG]) on prevention of NIHL. NAC and ginseng were selected because of safety, oral administration, and availability.
| Methods|| |
Trial design and participants
Male volunteer textile workers working in a textile factory in Tehran were included in this study. The workers enrolled to study if they were between 18 and 50 years old and were exposed to continuous noise more than 85 decibel (dB) for 8 h a day and did not use any hearing protection devices. The noise level was measured in different places using a calibrated sound level meter (Larson Davis Model 824, Provo, Utah, USA). Volunteer were not recruited if they:
- Were older than 50 years or <18
- Had a history of acoustic trauma, otological diseases or conditions that affected hearing,
- Had a history of taking nutrition supplements, vitamins and/or ototoxic drugs for the past 2 months,
- Had a history of head injury,
- Had a family history of congenital deafness, and
- Were smoking more than three cigarettes per day.
Before recruitment, otoscopy and tympanometry were performed to assess outer and middle ear in all participants.
From February to March 2013, a total of 51 patients were initially recruited and were randomly allocated to three equal groups, employing a random number generator software: NAC arm (Group N) who received NAC (ACC long, Hexal, Germany) 1200 mg/day for 14 days (once a day); ginseng arm (Group G) who received Panax ginseng (CA Meyer or KRG, Ginsana SA Bioggio/Switzerland) 200 mg/day for 14 days (once daily); and a control group who did not receive anything during these 14 days. NAC and ginseng were both administered orally as effervescent and immediate release tablets, respectively. All the participants worked in the same place and the sound level were equal for all of them (as measured by sound level meter).
At the 1 st day of the study, before taking drugs, pure tone audiometry (PTA) or conventional audiometry and high frequency audiometry (HFA) or extended HFA (EHFA) were done in an acoustic chamber for all 48 workers by an audiologist blinded to the study groups. All data were measured based on American National Standards Institute, 2004 standards.  PTA and HFA were measured with a high level resolution of 1 dB. Subsequently, on day 15, assessments were repeated prior to the work shift.
During intervention, we asked the participants to declare if they had experienced any unfavorable effect of each medication.
Pure tone audiometry was performed at 500, 1000, 2000, 4000, 6000 and 8000 frequencies using clinical audiometer (PC-based Interacoustic, Equinox AC 440 by TDH39 headphone , Denmark) and for HFA the test frequencies included 10,000, 12,500, 14,000 and 16,000 Hz using the same audiometer (PC-based Interacoustic, Equinox AC 440 by KOSS R80 headphone , Denmark) for both ears. Madsen GN otometrics was used for tympanometry.
The audiology team performed all the outcome assessments and was blinded to the allocation. Code breaking was not done only after the final assessment.
All experiments involving human subjects were carried out according to guidelines laid down in the declaration of Helsinki. University of Social Welfare and Rehabilitation Sciences board of ethics approved the study protocol. All participants gave written informed consent prior to enrolment. Details regarding safety of drugs were explained to the participants, although the randomization and allocation process was not revealed. This trial was registered at Iranian Registry of Clinical Trials (IRCT.ir) with IRCT registration number IRCT201301158698N9.
Analysis of variance (ANOVA) was performed to compare baseline characteristics of the sample by group. Furthermore, repeated measurement ANOVA was applied to compare the three groups in terms of audiometry at different frequencies. The mean changes in hearing threshold after noise exposure in three groups were assessed by one-way ANOVA and post-hoc test.
The associations between groups and hearing thresholds after 2 weeks (on day 15) were assessed using linear regression analysis. Three separate analyses were carried out to establish if these associations were modified by level of noise.
Statistical analyses were performed using the statistical package for social sciences (SPSS), version 18.0 release for Microsoft Windows (SPSS Inc., Chicago, Illinois, USA). In all tests, a P < 0.05 was considered as statistically significant.
| Results|| |
Fifty-one participants were studied for eligibility, of which 48 were enrolled and randomized in the three study arms. Three volunteers were excluded because of audiologic and/or otologic disorders. Hearing threshold of remaining participants were analyzed.
The mean age of workers was 39.12 ± 5 years (ranged from 28 to 50 years). The average of working age (noise exposure) was 14.48 ± 6 years. Baseline characteristics (age and the working age) of participants and baseline hearing thresholds of both ears were similar in three groups [Table 1]. Although no significant difference between pre- and post-exposure hearing threshold was observed in the N and G groups, exposure to noise significantly increased hearing threshold in the control group [Figure 1], [Figure 2] and [Figure 3].
|Figure 1: Comparison of hearing threshold between pre-and post-noise exposure in three groups at 4 kHz|
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|Figure 2: Comparison of hearing threshold between pre-and post-noise exposure in three groups at 6 kHz|
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|Figure 3: Comparison of hearing threshold between pre-and post-noise exposure in three groups at 16 kHz|
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[Table 2] shows the comparison of mean of change of hearing threshold after noise exposure between three groups at 4, 6, and 16 kHz. As the three groups were significantly different in postexposure hearing threshold, post-hoc test was applied to exactly spot the different groups. The results suggested significant differences in hearing threshold at 4 kHz between all three groups. At 6 and 16 kHz, however, the hearing thresholds of G and N groups had no significant differences, but were both significantly different with that of the control group [Figure 1], [Figure 2] and [Figure 3].
|Table 2: Comparison of mean of change of hearing threshold after noise exposure between three groups|
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Linear regression adjusted for hearing threshold before noise exposure and interaction between group and hearing threshold before noise exposure revealed that both ginseng and NAC had preventive effects on hearing loss of both ears at 4, 6, and 16 kHz.
Using control as the reference group, regression model in NAC and ginseng groups at of 4, 6 and 16 kHz frequencies show:
At 4 kHz:
Post = 2.95+ (−2.86) NAC + (−1.87) ginseng + 0.96 (Pre)
At 6 kHz:
Post = 2.63+ (−2.54) NAC + (−1.65) ginseng + 0.97 (Pre)
At 16 kHz:
Post = 4.21+ (−2.34) NAC + (−1.57) ginseng + 0.95 (Pre)
Linear regression analysis conducted revealed that the baseline hearing thresholds was positively associated with the second hearing thresholds (after 14 days) at 4, 6 and 16 kHz (P < 0.001).
It means that for each dB increase in before hearing threshold, the estimated after thresholds decreased by 2.86 for NAC, and decreased 1.87 for ginseng at 4 kHz. For each dB increase in before hearing threshold, the estimated after thresholds decreased by 2.54 for NAC, and decreased 1.65 for ginseng at 6 kHz. At 16 kHz, for each dB increase in baseline before hearing threshold, the estimated after thresholds decreased by 2.34 for NAC, and decreased 1.57 for ginseng.
| Discussion|| |
Based on our results, oral administration of either NAC (1200 mg/day) or ginseng (200 mg/day) significantly reduced noise-induced temporary threshold shift (TTS) at 4, 6 and 16 kHz frequencies after 14 days. The reduction was more prominent in NAC group than in the ginseng group in significant frequencies.
When the ear exposed to loud or intense noise over time, some mechanisms occur to injury cochlea and induce hearing loss. Previous researches emphasized physical, morphological and mechanical mechanisms of NIHL; , modern studies probe the molecular and metabolical mechanisms of hair cell damage. ,
There are various causes of noise-induced cochlear injury, so different kinds of hearing loss may occur including - TTS or permanent threshold shift (PTS).
Mechanisms of PTS by cochlear origin appeared to be death of hair cells (OHCs and IHCs), primary afferent neurons, or both. The exact mechanism of the noise-induced TTS is not clearly defined; ,,, recent studies stated ROS formation and oxidative stress as the main metabolic causes of TTS. , ROS are generated as a byproduct of mitochondrial respirations. There is a delay in free radical formation, peaking 7-10 days following noise exposure  so we continued use of these supplements (NAC and ginseng) for 2 weeks.
Glutathione is often referred to the body's master of antioxidants, reacting directly with oxidants (ROS), inhibit oxidation of the molecules. GSH has an important role in limiting noise-induced cochlear damage. 
N-acetyl-cysteine, known as Mucamist, is a free radical scavenger and a precursor of GSH which can neutralize noise  and increases GSH production. 
Pretreatment with NAC in animal studies demonstrated a significant reduction of noise-induced PTS, OHC, and IHC loss.  Hence, it may have same effects on noise-induced TTS, which was the primary endpoint of our study.
Besides animal studies, some clinical trials have done to evaluate NAC effects in attenuating NIHL. In a study conducted by Kramer et al., 31 subjects with normal hearing tests were administrated orally 900 mg of NAC or placebo, before participating in a club. However, no significant difference was seen in TTS between two groups.  There are some discrepancies between this study and ours including lower dosage of NAC and the shorter duration of NAC administration single dose versus 14 days in that study.
Another randomized study used 900 mg NAC 3 times a day for 14 days during weapon training. Results demonstrated safety of NAC and positive effects on PTS induced noise. 
A cross over clinical trial in 53 (placebo-controlled) steel manufacturing workers exposed to 88.4-89.4 dB showed that orally administration of 1200 mg/day NAC for 14 days reduced induced noise-TTS at high frequencies (3, 4 and 6 kHz). 
Korean red ginseng or Panax ginseng CA Meyer has anti-ROS and apoptotic property and therefore play a role in preventing of NIHL. Saponin and ginsenoside have an anti-oxidative effect. ,
Pretreatment with ginseng extract attenuated hydrogen peroxide-induced oxidative stress and apoptosis in human neuroblastoma cells.  Until the present time, some animal studies have been conducted in preventing effect of ginseng on NIHL.
Korean red ginseng fed to mice for 3 days after noise exposure of 110 dB for 3 h to induce TTS. Fast recovery demonstrated in mice fed KRG 1 h and 1 day after noise exposure. Eight-oxoguanine (a known ROS indicator after noise exposure) was not observed in stria vascularis of mice fed by KRG compared with the control group, results showed KRG inhibited TTS-induced HL. 
It is possible that KRG might be useful in preventing hearing damage in patients exposed with noise. 
The results of linear regression analysis will help researchers to evaluate the dose-response of drugs and to find the most effective drug in prevention of hearing loss (in NIHL workers) in further studies.
Results also showed TTS reduction by NAC in this study was more prominent than ginseng. It may be related to different mechanisms and discrepancy in their equal dosage of antioxidant effects.
Until date, no clinical trials intervention of ginseng performed on NIHL. However, it is limited to generalize these findings because of the small numbers of included subjects.
| Conclusion|| |
N-acetyl-cysteine and ginseng as antioxidant drugs showed to have preventive effects on NIHL. This beneficial effect was more pronounced for NAC. Therefore, targeting the molecular mechanisms in the prevention of NIHL should be encouraged in clinical practice. However, larger clinical trials are needed to be performed in this aspect.
| Acknowledgments|| |
The authors would like to thank Shaia Darman Novin Company and the staffs of a textile factory who participated in the study. This article was derived of PhD dissertation in Audiology course at University of Social Welfare and Rehabilitation Sciences, Tehran.
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Dr. Yones Lotfi
Department of Audiology, University of Social Welfare and Rehabilitation Sciences, Velenjak, P.O. Box 1985713834, Tehran
Source of Support: This study was funded by University of Social Welfare and Rehabilitation Sciences,, Conflict of Interest: None
Clinical trial registration IRCT201301158698N9.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]