Metabolomic Study On The Health Effects Of Occupational Noise

Background and purpose Occupational noise is the sound formed in the production process with irregular frequency and intensity.It exists in various sorts of producing departments and brings annoyance to workers.With the rapid development of global industry,occupational noise exposure in the workplace has become increasingly serious.Billions of workers are suffering from the health damages caused by the longterm occupational noise exposure.Many studies have proved that as a systematic stimulus,long-term occupational noise exposure will impair the auditory system,disturb the cardiovascular system,endocrine system and other non-auditory systems.At present,the epidemiological researches on the hazards of occupational noise are constantly progressing,but there also remain some inconsistent results.Meanwhile,there is a lack of metabolomic research on the health effects caused by occupational noise exposure.The purposes of this research are to analyze the influence of occupational noise on hypertension and hearing loss from the epidemiological perspective,screen the differentially expressed small molecule metabolites in human samples and animal samples through liquid chromatography-mass spectrometry,and analyze the related metabolic pathways.Providing a preliminary basis for analyzing the adverse health effects and the relevant biomarkers of occupational noise exposure.Methods 1.According to the inclusion and exclusion criteria,3001 workers from 3 manufacturing enterprises in Jiangsu Province were selected as study subjects.The basic characteristics and health examination information of the subjects were collected.The occupational noise level at workplace was obtained from the company records measured by qualified institutes.Occupational noise exposure was defined as exposed to the normalized continuous A-weighted sound pressure level equivalent to an 8hworking-day of 80 d B(A)or above for at least a year.All the subjects were divided into noise exposure group and control group based on the occupational history.The prevalence of hypertension and hearing loss between the two groups was compared.The relevant analysis of cumulative exposure time with hypertension and hearing loss was performed by using multivariate logistic regression after the adjustment of potential confounders.2.Liquid chromatography-mass spectrometry was utilized in this research.The occupational noise exposure group and the control group were matched in accordance with the basic information such as age,gender,BMI,smoke status and drink status.112 pairs of serum samples were collected in total,of which 40 pairs were used for non-targeted metabolomics analysis to screen differential metabolites and related pathways caused by noise exposure.72 pairs of serum samples were used for targeted verification to obtain the specific small molecule metabolites and correlative metabolic pathways that related to the occupational noise exposure.3.The broadband noise was used to simulate occupational noise for constructing acute noise exposure rat model(90d B SPL,8h per day for 2 weeks)and subacute noise exposure rat model(85d B SPL,8h per day,5d per week for 6 weeks).After the exposure,the body weight,organ coefficient,ABR threshold,blood pressure and blood lipid biochemical indicators of rats were detected respectively.Serum and urine samples of the rats were collected for non-targeted metabolomics analysis to find the changes in the level of small molecule metabolites generated by noise exposure,explore the potential pathways,compare the similarities and differences of the metabolites and metabolic pathways between human samples and rat samples.Results 1.The epidemiological study on the health effects of occupational noise exposure discovered that the prevalence of hypertension in noise-exposed workers(26.3%)was higher than that in control workers(16.9%),and the difference was statistically significant(P<0.05).In the participants who underwent the pure tone audiometry,the exposure group had a significantly increased prevalence of hearing loss(13.7%)than control group(9.9%)(P<0.05).For relationship between occupational noise and hypertension,it was found that the risk of hypertension in exposure group was higher than that in the control group after adjusting the potential confounders.And this association was more pronounced among the exposure group with at least 11 years exposure duration(OR=1.987,95%CI=1.511-2.614).For relationship between occupational noise and hearing loss,compared with control group,the risk of hearing loss significantly increased in the exposure group with at least 11 years exposure duration(OR=2.697,95%CI=1.750-4.156).2.The results of human serum metabolomics analysis indicated that 17 differential metabolites were identified in 40 pairs of samples by non-targeted serum metabolomics,mainly glycerophospholipids,fatty acids,steroids and their derivatives,which may be involved in glycerophospholipid metabolism,arachidonic acid metabolism and linoleic acid metabolism.The targeted metabolomics analysis in 72 pairs found that the change trends of 9 identified metabolites were consistent with before and the potential pathways involved were glycerophospholipid metabolism and arachidonic acid metabolism.3.The acute and subacute noise exposure rat models were constructed.The results suggested that both acute and subacute noise exposure caused an increased ABR threshold of rats at 32 k Hz(P<0.001),but no significant effects of noise exposure on the body weight and blood pressure were observed.The differences in blood lipid levels between acute noise exposure group and control group were not statistically significant.However,compared with the control group,the levels of serum cholesterol,triglyceride,and high-density lipoprotein in rats with subacute noise exposure were obviously increased(P<0.05).The results of metabolomics analysis indicated that,compared with the control group,there were 15 and 16 differential metabolites in serum and urine of the rats that exposed to acute noise,which may be related to the glycerophospholipid metabolism,citric acid cycle,phenylalanine metabolism,glycine,serine and threonine metabolism.Meanwhile,there were 23 and 12 differential metabolites in serum and urine of the rats that exposed to subacute noise,and the potential metabolic pathways including glycerophospholipid metabolism,phenylalanine metabolism and tyrosine metabolism.Furthermore,the glycerophospholipid metabolism and phenylalanine metabolism were disordered in both two exposure groups.Conclusion 1.The epidemiological study on the health effects of occupational noise exposure pointed that longterm exposure to occupational noise is associated with the increased risk of hypertension and hearing loss.2.The results of non-targeted screening and targeted verification of serum metabolomics in human samples indicated that occupational noise exposure can change the level of 9 metabolites which may participate in the glycerophospholipid metabolism and arachidonic acid metabolism,then interfere with the steady-state metabolic process.3.The results of animal experiments found that both acute and subacute noise exposure can increase the hearing threshold of rats.The subacute noise exposure can also interfere with the blood lipid levels of rats.Furthermore,acute noise exposure induced alterations in the level of 15 and 16 metabolites in serum and urine,subacute noise exposure changed the level of 23 and 12 metabolites in serum and urine,the related pathways were energy metabolism,lipid metabolism and amino acid metabolism.