Before intervention, mean MDA, SOD and TAC were 27.52 (7.46) nmol/ml, 58.84 (10.44) U/ml and 2.57 (0.67) mM respectively. After intervention, mean MDA, SOD and TAC were 24.57 (7.58) nmol/ml, 63.46 (11.02) U/ml and 2.70 (0.84) mM respectively. Since there is no commonly acknowledged normal range for oxidative stress parameters, the levels observed among the control groups are usually considered as the basis for comparison. It must be noted that due to budget limitations, regulations of the manufacturing plant and moral considerations regarding sampling, it was not possible to include employees from office environments as controls (no noise exposure), which raises the issue of exposure levels.
In a previous study by the authors, potential biomarkers involved in exposure to crystalline silica were investigated in an insulation manufacturing company. In that study, mean serum MDA was 8.26 (4.65) nmol/ml in the control group (office employees) , while this was significantly higher at 22.48 nmol/ml among the participants of the present study. Joshaghani and Shafe’i conducted a study in order to determine if serum superoxide dismutase levels and red blood cells have any relationship with serum homocysteine among patient with myocardial infarction. They report mean serum SOD among the control group (selected among healthy candidates) to be 8.44 (6.24) U/ml  while this was significantly higher at 61.28 U/ml among the participants of the present study. Prohan et al. conducted a study aimed at determining dietary and serum TAC levels and its relationship with depression among men. Mean TAC levels in their control group was 1.92 (0.34) mM  which is higher than that measured among the participants of the presents study at 1.64 nmol/ml.
The Effects of Noise Exposure on Stress Oxidative Parameters
Oxidant and anti-oxidant levels may differ depending on exposure duration, type of exposure and its intensity. But in general, increased oxidative stress during exposure is usually accompanied by a steady rise in anti-oxidant mechanisms . The results of the partial correlation test (while controlling for demographic variables) showed no significant correlation between exposure to noise and oxidative stress parameters, except for SOD activity which was statistically significant (R=-0.242, P = 0.042). A weak inverse relationship was observed between exposure levels and TAC and SOD activity, while MDA levels had a weak but direct relationship with exposure levels. As per the univariate analysis of variance, exposure to noise had a significant relationship with TAC only (P = 0.001), with a single unit increase in noise levels resulting in a 0.05 unit decrease in TAC. Noise exposure had a decremental effect on SOD activity and an incremental effect on MDA levels.
Elsayed & Gorbunov (2003). state that the oxidative stress caused by exposure to high levels of noise can reduce TAC which is followed by lipid peroxidation . Haghighat et al. showed that acute exposure to noise causes increases in 8-hydroxy2, deoxy guanosine and MDA as well as decreases in Glutathione (GSH), catalase (CAT) and SOD activity . Hosseinabadi et al. report that exposure to noise among workers occupied in the food industry increased the number of free radicals released while also increasing MDA levels depending on the increase in noise exposure. Their results show that MDA was higher in the exposure group at 19.96 (2.55) nmol/ml compared to the control group at 18.04 (2.41) nmol/ml with the difference being statistically significant (P > 0.001) (. Additionally, SOD activity was higher in the exposure group at 15.68 (2.01) U/ml compared to the control group at 13.57 (1.81) U/ml, but this difference was not statistically significant. According to their regression model, among the demographic and noise variables, noise level was the most important predictor of MDA levels (B = 0.48, P = 0.033), SOD activity (B=-0.34, P = 0.068) and TAC (B = 0.11, P = 0.001). Mean MDA levels and SOD activity among the participants of the present study were higher than that reported by Bagheri et al. in their study. Also, the effect of noise on oxidative stress parameters was only significant in the case of TAC, with the effect of noise on MDA being incremental while its effect on SOD and TAC was decremental. The reason for the differences between these two studies may be due the fact that the participants of the present study were simultaneously exposed to various physical and chemical stressors at varying intensities.
Yildirim et al. also report that MDA levels among textile workers exposed to 105 dBA noise was 2.17 (1.09) nmol/ml compared to the control group at 1.37 (0.50) nmol/ml, with the difference being statistically significant . Demirel et al. (2019) investigated the effects of noise on oxidative stress parameters in rats. Their results showed that MDA levels and Glutathione were significantly higher after the experiment. This suggests that the effects of noise exposure are not limited to the auditory system and may affect the whole body leading to oxidative stress . The inverse relationship between level of exposure to noise and SOD as well as TAC mean that with increased exposure, anti-oxidant capacity is reduced since these two parameters determine the anti-oxidant defense system of the body. Under normal conditions, the formation of free radicals is usually the result of cellular processes such as the mitochondrial respiratory chain and is controlled by the enzymatic and non-enzymatic defense mechanism of the body. When the body is exposed to an oxidative agent, the formation of free radicals in the body is increased which stimulates the anti-oxidant defense system of the body. In order to control the chain reactions of these free radicals, anti-oxidants step in with various mechanisms and combat the free radicals. By giving a hydrogen atom to the free radicals, the anti-oxidant itself is used up and the oxidative chain reactions are mitigated and oxidative damage to tissue is prevented.
Prolonged exposure to high intensity stressors can lead to uncontrolled lipid peroxidation beyond the capacity of the immune system. This reduces enzymatic activity due to its sensitivity to damage from the oxidative system which can result in reduced TAC. The increased oxidative stress observed in the present study may be due to various issues such as increases in general oxidations, reduction in the creation of anti-oxidants, the inability of the cell to recover from oxidative damage as well as damage caused to the cell from ROSs .
Keep in mind that during exposure to oxidative agents, the anti-oxidant defense system attempts to maintain the balance between oxidants and anti-oxidants. Initially, the anti-oxidant situation in the body changes and when the anti-oxidant system is unable to maintain redox, damage to macro molecules and the onset of lipid peroxidation occurs. Evaluating oxidative parameters in the present study reveals that among the various exposure groups, the amount of exposure was so high as to stimulate an anti-oxidant response within the body. There are a number of studies that have evaluated oxidative stress parameters as well as enzymatic activity such as glutathione peroxidase, superoxide dismutase and catalase in response to exposure to physical agents (such as noise). However, most studies in this regard look at oxidative stress in response to exposure to chemical agents or various disorders such as diabetes, Alzheimer’s disease, high blood pressure, cardiovascular disorders and cognitive function among human subjects as well as laboratory scale studies on animals. Evaluation of these studies is outside the scope and aim of the present paper and thus, there were limitations regarding the comparison and discussion of results obtained regarding changes in TAC. Still, in various disorders and under physiologically stressful situation, research suggests changes in TAC which are usually decremental. Keshvari et al. looked at oxidative stress biomarkers in workers of a ceramics manufacturing plant. Their results show a significant reduction in TAC and total serum thiol groups among workers compared to the control group .
The Effects of Nutritional supplementation on Stress Oxidative Parameters
Regarding supplement use and its effect on oxidative stress parameters, results show that the difference in MDA levels before and after intervention was only significant in the Vitamin E group and was not significant in any other supplement group. After intervention, mean serum MDA levels had gone down in all supplement groups. Differences in mean serum SOD levels before and after intervention was only significant in the Vitamin E + Omega 3 supplement group and was not significant in any other supplement group. After intervention, mean serum SOD levels had gone up in all supplement groups. The differences in TAC before and after intervention was not significant in any of the supplement groups but overall, serum TAC had increased after intervention among the participants.
Based on univariate analysis of variance, the use of ω − 3 can have a significant decremental effect on MDA levels. The use of Vitamin E + ω − 3 on MDA levels was decremental but not statistically significant. Supplement use had an incremental effect on SOD levels in all supplement groups but this was only significant in the Vitamin E + ω − 3 group. Supplement use in all groups had an incremental effect on TAC with the largest effect being observed in the Vitamin E + ω − 3 group but none were statistically significant. Similar to the presents study, a significant reduction in MDA levels after daily ω − 3 supplement use among those suffering from Atherosclerosis ) and Hemodialysis  have been observed. Fazlian et al. showed in their systematic meta-analysis review that the use of ω − 3 fatty acids can cause a significant reduction in MDA levels .
One of the important targets of oxidative stress is lipid profiles. Oxidation of lipid profiles leads to increased production of MDA as a secondary by-product. The positive effects of ω-3 consumption on MDA levels may be due to its effect on improved lipid profiles and reduced lipid peroxidation. Lipid peroxidation is mediated by free radical compounds and thus the reduction in MDA production resulting from ω-3 use may be due to its anti-inflammatory properties . There are a number of studies that agree with the finding of the present study regarding the positive effects of ω-3 and vitamin E supplement use on the anti-oxidant system. Rahmani et al. (2017) have shown that a 12-week ω-3 and vitamin E supplement regiment in woman suffering from polycystic ovary syndrome resulted in a significant increase in plasma TAC (+ 89.4 ± 108.9 vs. +5.9 ± 116.2 mmol/L, P = 0.003) as well as a significant decrease in MDA levels compared with the placebo (-0.3 ± 0.4 vs. -0.008 ± 0.6 µmol/L, P = 0.01) . Liu et al. (2015) investigated the effects of Omega 3, Omega 6 and vitamin E consumption on the anti-oxidant performance of wild boars . Their results show that using 400mg/kg of vitamin E (compared to 200mg/kg) increased SOD and TAC anti-oxidant parameters while reducing MDA levels. Lie et al. state that using ω-3 and ω-6 at a ratio of 6/6 as well as 400mg/kg of vitamin E can improve anti-oxidant performance (38). Similarly, another study conducted on pregnant women shows that a 6-week consumption of vitamin E (400 units) and Omega 3 (1000mg) resulted in a significant increase in plasma TAC (224.9 mmol/L vs. 136.1 mmol/L) as well as a significant reduction in MDA (0.9 µmol/L vs 6.4 mmol/L) compared to the placebo .
Vitamin E is soluble in fat and can be found in various foods such as wheat, meat, plant-based oils, eggs and leafy vegetables. Vitamin E is also useful in curing many disorders. In humans and mice, vitamin E is converted to alpha-Tocopherol metabolite. Vitamin E (Tocopherol) plays a protective role in preventing free radicals from destroying the cell membrane . The benefits of Omega 3 fatty acids in preventing cardiovascular disorders are also clear. Evidence has been mounting in recent years regarding the positive effects of using Omega 3 fatty acids including studies on animals. However, these studies are not conclusive and further investigation is required. It is important to maintain a suitable daily intake of fatty acids since these acids (such as DHA and EPA) are not naturally created in the human body. Omega 3 fatty acid supplements are widely available, safe and cheap which makes them a highly valuable solution .
It is not easy to arrive at a definitive conclusion in the present study regarding the effects of exposure to high level noise on oxidative stress parameters as well as the role of supplementation in improving anti-oxidant performance. This is mainly because even though the calculated sample size and the requirements for entry were all determined with confounding factors in mind, it is not feasible to control all factors that may be influential in this regard. This is usually the case when it comes to human trials and field studies. This does not mean that the testing of theories in field studies is not without its merit as these studies are better at reflecting real world conditions . Overall, there are some limiting factors that make it hard to make conclusions about the effects of exposure to high level noise on oxidative stress parameters as well as the role of supplement use which include:
The lack of suitable control groups from office environments with no noise exposure due to budget constraints.
Natural daily variations in oxidative stress parameters.
Limitations in repeating self-monitoring due to budget constraints, strict role of the industry and ethical issues.
Inability to biologically monitor the supplements used due to budget constraints.
Various influential factors such as harmful chemical agents (polycyclic aromatic hydrocarbons or heavy metals), physical agents (electromagnetic fields, vibration and heat stress) as well as psychological stressors and background disorders.
Limitations and sample drop caused by the Covid-19 pandemic.
Lack of historical records regarding oxidative stress parameters of the participants at the beginning of their employment.
The inability to homogenize the participants in terms of demographic characteristics such as age, employment duration and BMI.
The inability to remove participants who are smokers or those who use recreational drugs due to a lack of suitable replacements and the resulting sample size.