Abstract
Noise-induced hearing loss (NIHL) remains a leading occupational related disease and is a serious public health problem. Hence, the identification of potential biomarkers for NIHL prevention and diagnosis has become an urgent work. To discover potential metabolic biomarkers of NIHL, plasma metabolomics analysis in 62 NIHL patients and 62 normal hearing controls was performed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF MS). Orthogonal partial least square-discriminant analysis (OPLS-DA) model was applied to distinguish metabolite profile alterations in plasma samples between the two groups. The metabolites with a variable importance of projection (VIP) value > 1 and P value < 0.05 were considered to be potential metabolic biomarkers. KEGG database was performed to explore the involved pathways of potential biomarkers. Three autophagy-related genes (PI3K, AKT, and ATG5) were selected for further verification, and mRNA levels were detected using RT-qPCR analysis. Twenty plasma metabolites with VIP > 1 and P < 0.05 were significantly altered between the two groups. Totally, seven metabolic pathways involving the glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, autophagy pathway, choline metabolism, the alpha-linolenic acid metabolism and linoleic acid metabolism, and retrograde endocannabinoid pathway were significantly related to NIHL. Furthermore, verification by RT-qPCR suggested that the mRNA expression levels of PI3K and AKT along with ATG5 were significantly lower in the NIHL patients compared with controls. In summary, the present study provides the first evidence that the identified aberrantly altered metabolites may be the potentially valuable biomarkers of NIHL for occupational noise-exposed workers. Autophagy signal pathway may be involved in the occurrence and development of NIHL. Moreover, this present study may be helpful to further better understand the metabolic changes in NIHL and be helpful for the understanding of pathogenic mechanism.
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Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
References
Babisch W (2006) Transportation noise and cardiovascular risk: updated review and synthesis of epidemiological studies indicate that the evidence has increased. Noise Health 8:1–29
Babisch W, Beule B, Schust M, Kersten N, Ising H (2005) Traffic noise and risk of myocardial infarction. Epidemiology 16:33–40
Basner M, Babisch W, Davis A, Brink M, Clark C, Janssen S, Stansfeld S (2014) Auditory and non-auditory effects of noise on health. Lancet 383:1325–1332
Bianco F, Fredianelli L, Lo Castro F, Gagliardi P, Fidecaro F, Licitra G (2020) Stabilization of a p-u sensor mounted on a vehicle for measuring the acoustic impedance of road surfaces. Sensors (Basel):20
Browning RG, Olson DW, Stueven HA, Mateer JR (1990) 50% dextrose: antidote or toxin? Ann Emerg Med 19:683–687
Chen J, Yuan H, Talaska AE, Hill K, Sha SH (2015) Increased sensitivity to noise-induced hearing loss by blockade of endogenous PI3K/Akt signaling. J Assoc Res Otolaryngol 16:347–356
Chen C, Li H, Niu Y, Liu C, Lin Z, Cai J, Li W, Ge W, Chen R, Kan H (2019) Impact of short-term exposure to fine particulate matter air pollution on urinary metabolome: A randomized, double-blind, crossover trial. Environ Int 130:104878
Cheriyath P, Gorrepati VS, Peters I, Nookala V, Murphy ME, Srouji N, Fischman D (2010) High total bilirubin as a protective factor for diabetes mellitus: an analysis of NHANES data from 1999 - 2006. J Clin Med Res 2:201–206
Cvetkovic Z, Milosevic M, Cvetkovic B, Masnikosa R, Arsic A, Petrovic S, Vucic V (2017) Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients. Leuk Res 54:39–46
de León G, Del Pizzo A, Teti L, Moro A, Bianco F, Fredianelli L, Licitra G (2020) Evaluation of tyre/road noise and texture interaction on rubberised and conventional pavements using CPX and profiling measurements. Road Materials and Pavement Design 21:S91–S102
Del Pizzo A, Teti L, Moro A, Bianco F, Fredianelli L, Licitra G (2020) Influence of texture on tyre road noise spectra in rubberized pavements. Appl Acoust 159
Dimakopoulou K, Koutentakis K, Papageorgiou I, Kasdagli MI, Haralabidis AS, Sourtzi P, Samoli E, Houthuijs D, Swart W, Hansell AL, Katsouyanni K (2017) Is aircraft noise exposure associated with cardiovascular disease and hypertension? Results from a cohort study in Athens, Greece. Occup Environ Med 74:830–837
Dratva J, Phuleria HC, Foraster M, Gaspoz JM, Keidel D, Kunzli N, Liu LJ, Pons M, Zemp E, Gerbase MW, Schindler C (2012) Transportation noise and blood pressure in a population-based sample of adults. Environ Health Perspect 120:50–55
Erickson LC, Newman RS (2017) Influences of background noise on infants and children. Curr Dir Psychol Sci 26:451–457
Floegel A, Stefan N, Yu Z, Muhlenbruch K, Drogan D, Joost HG, Fritsche A, Haring HU, Hrabe de Angelis M, Peters A, Roden M, Prehn C, Wang-Sattler R, Illig T, Schulze MB, Adamski J, Boeing H, Pischon T (2013) Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes 62:639–648
Fracchiolla D, Zens B, Martens S (2017) In vitro reconstitution of Atg8 conjugation and deconjugation. Methods Enzymol 587:377–390
Fujimoto C, Iwasaki S, Urata S, Morishita H, Sakamaki Y, Fujioka M, Kondo K, Mizushima N, Yamasoba T (2017) Autophagy is essential for hearing in mice. Cell Death Dis 8:e2780
Fujita T, Yamashita D, Irino Y, Kitamoto J, Fukuda Y, Inokuchi G, Hasegawa S, Otsuki N, Yoshida M, Nibu K (2015) Metabolomic profiling in inner ear fluid by gas chromatography/mass spectrometry in guinea pig cochlea. Neurosci Lett 606:188–193
Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W, Moghadam AR, Kashani HH, Hashemi M, Owji AA, Los MJ (2014) Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol 112:24–49
Halperin D (2014) Environmental noise and sleep disturbances: a threat to health? Sleep Sci 7:209–212
Hayashi K, Suzuki Y, Fujimoto C, Kanzaki S (2020) Molecular mechanisms and biological functions of autophagy for genetics of hearing impairment. Genes (Basel) 11
He J, Zhu Y, Aa J, Smith PF, De Ridder D, Wang G, Zheng Y (2017) Brain metabolic changes in rats following acoustic trauma. Front Neurosci 11:148
Heras-Sandoval D, Perez-Rojas JM, Hernandez-Damian J, Pedraza-Chaverri J (2014) The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal 26:2694–2701
Heritier H, Vienneau D, Foraster M, Eze IC, Schaffner E, Thiesse L, Rudzik F, Habermacher M, Kopfli M, Pieren R, Brink M, Cajochen C, Wunderli JM, Probst-Hensch N, Roosli M, group SNCs (2017) Transportation noise exposure and cardiovascular mortality: a nationwide cohort study from Switzerland. Eur J Epidemiol 32:307–315
Hidalgo FJ, Nogales F, Zamora R (2005) Changes produced in the antioxidative activity of phospholipids as a consequence of their oxidation. J Agric Food Chem 53:659–662
Hirsch HA, Iliopoulos D, Joshi A, Zhang Y, Jaeger SA, Bulyk M, Tsichlis PN, Shirley Liu X, Struhl K (2010) A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases. Cancer Cell 17:348–361
Horsfall LJ, Nazareth I, Petersen I (2012) Cardiovascular events as a function of serum bilirubin levels in a large, statin-treated cohort. Circulation 126:2556–2564
Huang Q, Hu D, Wang X, Chen Y, Wu Y, Pan L, Li H, Zhang J, Deng F, Guo X, Shen H (2018) The modification of indoor PM2.5 exposure to chronic obstructive pulmonary disease in Chinese elderly people: a meet-in-metabolite analysis. Environ Int 121:1243–1252
Leamy AK, Egnatchik RA, Shiota M, Ivanova PT, Myers DS, Brown HA, Young JD (2014) Enhanced synthesis of saturated phospholipids is associated with ER stress and lipotoxicity in palmitate treated hepatic cells. J Lipid Res 55:1478–1488
Licitra G, Fredianelli L, Petri D, Vigotti MA (2016) Annoyance evaluation due to overall railway noise and vibration in Pisa urban areas. Sci Total Environ 568:1315–1325
Licitra G, Teti L, Cerchiai M, Bianco F (2017) The influence of tyres on the use of the CPX method for evaluating the effectiveness of a noise mitigation action based on low-noise road surfaces. Transp Res Part D: Transp Environ 55:217–226
Lie A, Skogstad M, Johannessen HA, Tynes T, Mehlum IS, Nordby KC, Engdahl B, Tambs K (2016) Occupational noise exposure and hearing: a systematic review. Int Arch Occup Environ Health 89:351–372
Liu C, Fuertes E, Tiesler CM, Birk M, Babisch W, Bauer CP, Koletzko S, von Berg A, Hoffmann B, Heinrich J, Giniplus GLIS (2014) The associations between traffic-related air pollution and noise with blood pressure in children: results from the GINIplus and LISAplus studies. Int J Hyg Environ Health 217:499–505
Masterson EA, Bushnell PT, Themann CL, Morata TC (2016) Hearing impairment among noise-exposed workers - United States, 2003-2012. MMWR Morb Mortal Wkly Rep 65:389–394
Miao L, Ji J, Wan L, Zhang J, Yin L, Pu Y (2019) An overview of research trends and genetic polymorphisms for noise-induced hearing loss from 2009 to 2018. Environ Sci Pollut Res Int 26:34754–34774
Miao L, Wang B, Ji J, Wan L, Yin L, Zhu B, Zhang J, Pu Y (2021a) CARD8 polymorphism rs2043211 protects against noise-induced hearing loss by causing the dysfunction of CARD8 protein. Environ Sci Pollut Res Int 28:8626–8636
Miao L, Wang B, Zhang J, Yin L, Pu Y (2021b) A functional SNP in miR-625-5p binding site of AKT2 3'UTR is associated with noise-induced hearing loss susceptibility in the Chinese population. Environ Sci Pollut Res Int
Miedema HME, Oudshoorn CGM (2001) Annoyance from transportation noise: relationships with exposure metrics DNL and DENL and their confidence intervals. Environ Health Perspect 109:409–416
Minetti M, Mallozzi C, Di Stasi AM, Pietraforte D (1998) Bilirubin is an effective antioxidant of peroxynitrite-mediated protein oxidation in human blood plasma. Arch Biochem Biophys 352:165–174
Minichilli F, Gorini F, Ascari E, Bianchi F, Coi A, Fredianelli L, Licitra G, Manzoli F, Mezzasalma L, Cori L (2018) Annoyance judgment and measurements of environmental noise: a focus on Italian secondary schools. Int J Environ Res Public Health 15
Monrad M, Sajadieh A, Christensen JS, Ketzel M, Raaschou-Nielsen O, Tjonneland A, Overvad K, Loft S, Sorensen M (2016) Residential exposure to traffic noise and risk of incident atrial fibrillation: a cohort study. Environ Int 92-93:457–463
Muzet A (2007) Environmental noise, sleep and health. Sleep Med Rev 11:135–142
Neghab M, Hosseinzadeh K, Hassanzadeh J (2015) Early liver and kidney dysfunction associated with occupational exposure to sub-threshold limit value levels of benzene, toluene, and xylenes in unleaded petrol. Saf Health Work 6:312–316
Ohlemiller KK, Wright JS, Dugan LL (1999) Early elevation of cochlear reactive oxygen species following noise exposure. Audiol Neurootol 4:229–236
Praticò FG, Anfosso-Lédée F (2012) Trends and issues in mitigating traffic noise through quiet pavements. Procedia Soc Behav Sci 53:203–212
Pudrith C, Dudley WN (2019) Sensorineural hearing loss and volatile organic compound metabolites in urine. Am J Otolaryngol 40:409–412
Sedlak TW, Saleh M, Higginson DS, Paul BD, Juluri KR, Snyder SH (2009) Bilirubin and glutathione have complementary antioxidant and cytoprotective roles. Proc Natl Acad Sci U S A 106:5171–5176
Seidler A, Wagner M, Schubert M, Droge P, Romer K, Pons-Kuhnemann J, Swart E, Zeeb H, Hegewald J (2016) Aircraft, road and railway traffic noise as risk factors for heart failure and hypertensive heart disease-a case-control study based on secondary data. Int J Hyg Environ Health 219:749–758
Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82:291–295
Son JH, Shim JH, Kim KH, Ha JY, Han JY (2012) Neuronal autophagy and neurodegenerative diseases. Exp Mol Med 44:89–98
Sorensen M, Hvidberg M, Hoffmann B, Andersen ZJ, Nordsborg RB, Lillelund KG, Jakobsen J, Tjonneland A, Overvad K, Raaschou-Nielsen O (2011) Exposure to road traffic and railway noise and associations with blood pressure and self-reported hypertension: a cohort study. Environ Health 10:92
Sorensen M, Andersen ZJ, Nordsborg RB, Becker T, Tjonneland A, Overvad K, Raaschou-Nielsen O (2013) Long-term exposure to road traffic noise and incident diabetes: a cohort study. Environ Health Perspect 121:217–222
Stansfeld SA, Berglund B, Clark C, Lopez-Barrio I, Fischer P, Ohrstrom E, Haines MM, Head J, Hygge S, van Kamp I, Berry BF, team Rs (2005) Aircraft and road traffic noise and children's cognition and health: a cross-national study. Lancet 365:1942–1949
Sun R, Xu K, Zhang Q, Jiang X, Man Z, Yin L, Zhang J, Pu Y (2018) Plasma metabonomics investigation reveals involvement of fatty acid oxidation in hematotoxicity in Chinese benzene-exposed workers with low white blood cell count. Environ Sci Pollut Res Int 25:32506–32514
Teti L, de León G, Del Pizzo A, Moro A, Bianco F, Fredianelli L, Licitra G (2020) Modelling the acoustic performance of newly laid low-noise pavements. Constr Build Mater 247:118509
van Kempen E, Babisch W (2012) The quantitative relationship between road traffic noise and hypertension: a meta-analysis. J Hypertens 30:1075–1086
Wang CW, Klionsky DJ (2003) The molecular mechanism of autophagy. Mol Med 9:65–76
Wang X, Liu L, Zhang W, Zhang J, Du X, Huang Q, Tian M, Shen H (2017) Serum metabolome biomarkers associate low-level environmental perfluorinated compound exposure with oxidative /nitrosative stress in humans. Environ Pollut 229:168–176
Wothge J, Belke C, Mohler U, Guski R, Schreckenberg D (2017) The Combined effects of aircraft and road traffic noise and aircraft and railway noise on noise annoyance-an analysis in the context of the joint research initiative NORAH. Int J Environ Res Public Health:14
Yamashita D, Jiang HY, Schacht J, Miller JM (2004) Delayed production of free radicals following noise exposure. Brain Res 1019:201–209
Yang Z, Klionsky DJ (2009) An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol 335:1–32
Ye G, Liu Y, Yin P, Zeng Z, Huang Q, Kong H, Lu X, Zhong L, Zhang Z, Xu G (2014) Study of induction chemotherapy efficacy in oral squamous cell carcinoma using pseudotargeted metabolomics. J Proteome Res 13:1994–2004
Yuan H, Wang X, Hill K, Chen J, Lemasters J, Yang SM, Sha SH (2015) Autophagy attenuates noise-induced hearing loss by reducing oxidative stress. Antioxid Redox Signal 22:1308–1324
Zacarias FF, Molina RH, Ancela JLC, Lopez SL, Ojembarrena AA (2013) Noise exposure in preterm infants treated with respiratory support using neonatal helmets. Acta Acust United Acust 99:590–597
Zhang J, Liu L, Wang X, Huang Q, Tian M, Shen H (2016) Low-level environmental phthalate exposure associates with urine metabolome alteration in a Chinese male cohort. Environ Sci Technol 50:5953–5960
Zheng W, Xie W, Yin D, Luo R, Liu M, Guo F (2019) ATG5 and ATG7 induced autophagy interplays with UPR via PERK signaling. Cell Commun Signal 17:42
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The authors thank every worker for their participations in this study.
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This study was supported by the Open Research Fund of State Key Laboratory of Bioelectronics, Southeast University.
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YP designed the research study. LM and BW performed the research and analyzed the data. LM drafted the manuscript. JZ; LY critically reviewed and revised the manuscript. All authors read and approved the final manuscript.
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Miao, L., Wang, B., Zhang, J. et al. Plasma metabolomic profiling in workers with noise-induced hearing loss: a pilot study. Environ Sci Pollut Res 28, 68539–68550 (2021). https://doi.org/10.1007/s11356-021-15468-z
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DOI: https://doi.org/10.1007/s11356-021-15468-z