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.

Highlights

  • Occupational noise, a common harmful factor that seriously affects the health of workers in the field of occupational health

  • The results indicated that the mRNA levels of three autophagy-related genes (PI3K, AKT and ATG5) were significantly decreased in Noise-induced hearing loss (NIHL) cases compared with controls

  • The results showed that NIHL patients had a significantly higher hearing threshold of high frequency in both ears (53.24 ± 13.01) compared with the controls (18.73 ± 3.96; P < 0.001)

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Summary

Introduction

Occupational noise, a common harmful factor that seriously affects the health of workers in the field of occupational health. The World Health Organization (WHO) has reported that about ten percent of the world’s population is exposed to high level of noise and is at risk of developing NIHL (Basner et al 2014). NIHL is an urgent health problem and has a strong impact on social economy and human health. NIHL is one of the leading occupational related disease in China, accounting for approximately one-sixth of the annual increase of occupational disease (Miao et al 2019). A number of studies were conducted, the specific pathogenesis underlying NIHL has still not been entirely illustrated.

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