Abstract
Noise pollution has become one of the important social hazards that endanger the auditory system of residents, causing noise-induced hearing loss (NIHL). Oxidative stress has a significant role in the pathogenesis of NIHL, in which the silent information regulator 1(SIRT1)/proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway is closely engaged. Ginsenoside Rd (GSRd), a main monomer extract from ginseng plants, has been confirmed to suppress oxidative stress. Therefore, the hypothesis that GSRd may attenuate noise-induced cochlear hair cell loss seemed promising. Forty-eight male guinea pigs were randomly divided into four groups: control, noise exposure, GSRd treatment (30 mg/kg Rd for 10d + noise), and experimental control (30 mg/kg glycerol + noise). The experimental groups received military helicopter noise exposure at 115 dB (A) for 4 h daily for five consecutive days. Hair cell damage was evaluated by using inner ear basilar membrane preparation and scanning electron microscopy. Terminal dUTP nick end labeling (TUNEL) and immunofluorescence staining were conducted. Changes in the SIRT1/PGC-1α signaling pathway and other apoptosis-related markers in the cochleae, as well as oxidative stress parameters, were used as readouts. Loss of outer hair cells, more disordered cilia, prominent apoptosis, and elevated free radical levels were observed in the experimental groups. GSRd treatment markedly mitigated hearing threshold shifts, ameliorated outer hair cell loss and lodging or loss of cilia, and improved apoptosis through decreasing Bcl-2 associated X protein (Bax) expression and increasing Bcl-2 expression. In addition, GSRd alleviated the noise-induced cochlear redox injury by upregulating superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, decreasing malondialdehyde (MDA) levels, and enhancing the activity of SIRT1 and PGC-1α messenger ribonucleic acid (mRNA) and protein expression. In conclusion, GSRd can improve structural and oxidative damage to the cochleae caused by noise. The underlying mechanisms may be associated with the SIRT1/PGC-1α signaling pathway.
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All data generated or analyzed during this study are available from the corresponding author on reasonable request. All materials are commercially available.
Abbreviations
- 3-NT :
-
3-Nitrotyrosine
- 4-HNE :
-
4-Hydroxy-4-hydroxynonenal
- ABR :
-
Auditory brainstem response
- AHL :
-
Age-related hearing loss
- Bcl-2 :
-
B-cell lymphoma-2
- Bax :
-
Bcl-2 associated X protein
- DAPI :
-
4,6-Diamino-2-phenylindole
- GO :
-
Gene ontology
- GSH-Px :
-
Glutathione peroxidase
- GSRd :
-
Ginsenoside Rd
- IgG :
-
Immunoglobulin G
- MDA :
-
Malondialdehyde
- NIHL :
-
Noise-induced hearing loss
- PBS :
-
Phosphate-buffered saline
- PBST :
-
Phosphate-buffered saline-Tween
- PGC-1α :
-
Proliferator-activated receptor-gamma coactivator 1α
- RNA :
-
Ribonucleic acid
- RNS :
-
Reactive nitrogen species
- ROS :
-
Reactive oxygen species
- SEM :
-
Scanning electron microscopy
- SIRT1 :
-
Silent information regulator 1
- SOD :
-
Superoxide dismutase
- TUNEL :
-
Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay
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Acknowledgements
Our deepest gratitude goes to colleagues from Senior Department of Otolaryngology & Head and Neck Surgery, Chinese PLA General Hospital, led by Prof. Shi-ming Yang and Department of Otolaryngology, Xijing Hospital, led by Prof. Jian-hua Qiu for their valuable technical support.
Funding
This work was supported by grants from the Major Military Project (grant number AWS14L009) and Key Researcher and Development Plan in Shaanxi (grant number 2018SF-252).
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XMC, YHL, YMC, and XCW conceived and designed the experiment methods. XMC and YHL drafted the manuscript. SFJ performed bioinformatic analysis. XMC and LLW performed phalloidin staining, SEM observation RT-qPCR, and western blot analysis. SFJ and XMX performed TUNEL staining. YHL and XMX performed immunofluorescence staining for 4-HNE and 3-NT. XMX examined SOD, MDA, and GSH-Px levels. XMC, SFJ, and LLW conducted the statistics. XMC and SFJ revised the manuscript. XCW takes responsibility for the integrity of the data and the accuracy of data analysis.
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Chen, Xm., Liu, Yh., Ji, Sf. et al. Protective effect of ginsenoside Rd on military aviation noise-induced cochlear hair cell damage in guinea pigs. Environ Sci Pollut Res 30, 23965–23981 (2023). https://doi.org/10.1007/s11356-022-23504-9
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DOI: https://doi.org/10.1007/s11356-022-23504-9