SOD mediates mitochondrial epigenetic regulation in NIHL

Area of Science:

• Environmental Health
• Epigenetics
• Otolaryngology

Background:

• Occupational noise exposure is a significant risk factor for hearing loss.
• Mitochondrial dysfunction and oxidative stress are implicated in noise-induced hearing loss (NIHL).
• Epigenetic modifications, such as DNA methylation, may play a role in NIHL pathogenesis.

Purpose of the Study:

• To investigate the association between mitochondrial DNA (mtDNA) D-loop region methylation and oxidative stress markers in workers with and without NIHL.
• To explore the relationship between mtDNA methylation, oxidative stress, and hearing thresholds.
• To identify potential epigenetic biomarkers for NIHL.

Main Methods:

• A cross-sectional study involving 150 workers divided into control, noise-exposed, and NIHL groups.
• Quantitative PCR following bisulfite conversion was used to assess mtDNA D-loop methylation.
• Real-time PCR measured mitochondrial DNA copy number (mtDNA-CN).
• Oxidative stress markers (SOD, GPX, TAS, MDA) were quantified using specific assays.

Main Results:

• NIHL cases exhibited lower superoxide dismutase (SOD) and higher malondialdehyde (MDA) levels compared to controls.
• The NIHL group showed significantly lower mtDNA D-loop methylation levels.
• Higher mtDNA copy number (mtDNA-CN) was observed in the NIHL group.
• D-loop methylation positively correlated with SOD and negatively with MDA.
• Mediation analysis suggested SOD mediates the link between D-loop methylation and hearing thresholds.

Conclusions:

• Noise-induced oxidative imbalance, characterized by reduced SOD, may lead to mtDNA D-loop hypomethylation, contributing to NIHL.
• mtDNA D-loop methylation patterns and oxidative stress markers may serve as preliminary biomarkers for NIHL.
• Epigenetic regulation of mtDNA could be a key mechanism in the development of occupational hearing loss.