Ginsenoside Rd Ameliorates Auditory Cortex Injury Associated With Military Aviation Noise-Induced Hearing Loss by Activating SIRT1/PGC-1α Signaling Pathway

Chen, Xuemin; Ji, Shuaifei; Liu, Yuhui; Xue, Xin-Miao; Xu, Jin; Gu, Zheng-Hui; Deng, Senlin; Liu, Chengdong; Wang, Han; Chang, Yao-Ming; Wang, Xiaocheng

doi:10.3389/fphys.2020.00788

Cited by 29 publications

(15 citation statements)

References 49 publications

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“…Previous results have demonstrated that GSRd can signi cantly reverse the increase in the auditory brainstem response threshold caused by noise stimulation (Supplementary Fig. 1) [35], which supports our initial hypothesis. The results of the GSRd GO enrichment analysis focused our attention on a molecule associated with the regulation of mitochondrial activity and oxidative stress, which is SIRT1 (Table 1).…”

Section: Resultssupporting

confidence: 89%

“…After detecting the hearing threshold levels [35], the animals were euthanized. The bilateral temporal bones of guinea pigs were removed, and the bilateral cochleae were separated immediately.…”

Section: Tissue Preparationmentioning

confidence: 99%

“…The protocols used in this study were conducted, as described by Chen et al [35]. RNAiso (TaKaRa, Kyoto, Japan) was added to the homogenized cochlear specimens to extract total ribonucleic acid (RNA), based on the manufacturer's instructions.…”

Section: Quantitative Real-time Polymerase Chain Reaction Analysismentioning

confidence: 99%

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Protective Effect of Ginsenoside Rd on Military Aviation Noise-Induced Cochlear Hair Cell Damage

Chen

Y²,

et al. 2021

Preprint

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Background Soldiers are often exposed to high-intensity noise produced by military weapons and equipment during activities, and the incidence of noise-induced hearing loss (NIHL) in many arms is high. Oxidative stress has a significant role in the pathogenesis of NIHL, and research has confirmed that ginsenoside Rd (GSRd) suppresses oxidative stress. Therefore, we hypothesized that GSRd may attenuate NIHL and cochlear hair cell loss, induced by military aviation noise stimulation, through the Sirtuin1/proliferator-activated receptor-gamma coactivator 1α (SIRT1/PGC-1α) signaling pathway.Methods Forty-eight male guinea pigs were randomly divided into four groups: control, noise stimulation, GSRd, and glycerol. The experimental groups received military helicopter noise stimulation 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 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.Results Loss of outer hair cells, more disordered cilia, prominent apoptosis, and elevated free radical levels were observed in the experimental groups. GSRd treatment markedly improved morphological changes and apoptosis through decreasing Bcl-2 associated X protein (Bax) expression and increasing Bcl-2 expression. In addition, GSRd upregulated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, decreased malondialdehyde (MDA) levels, and enhanced the activity of SIRT1 and PGC-1α messenger ribonucleic acid and protein expression.Conclusion GSRd can improve structural and functional damage to the cochleae caused by noise. The underlying mechanisms may be associated with the SIRT1/PGC-1α signaling pathway.

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Section: Resultssupporting

confidence: 89%

Section: Tissue Preparationmentioning

confidence: 99%

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Protective Effect of Ginsenoside Rd on Military Aviation Noise-Induced Cochlear Hair Cell Damage

Chen

Y²,

et al. 2021

Preprint

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“…Free radicals and oxidative stress also play essential roles in the pathogenesis of NIHL (Liu et al, 2016 , 2019c ; He et al, 2017 ; Li et al, 2018b ; Chen et al, 2020 ). Cytochrome-c is a biomarker of oxidative stress, which serves as an indicator of oxidative damage (Yamasoba et al, 2005 ).…”

Section: Resultsmentioning

confidence: 99%

“…The activation of caspase-3, known to trigger widespread damage and degeneration, can also modulate synaptic function (Imbriani et al, 2019 ). Likewise, Bcl-2 expression is reduced, whereas Bax is increased in IHCs after noise exposure (Chen et al, 2020 ). Therefore, we investigated the expression of mitochondrial-dependent damage markers, such as Bax and cytochrome-c. As shown in Figure 3C , an increase in the ratio of Bax/Bcl-2 (1.19 ± 0.42 vs. 4.13 ± 0.85, for B6 and CBA mice, respectively, unpaired t- test, P = 0.036) and cytochrome-c release (0.85 ± 0.16 vs. 1.69 ± 0.25, for B6 and CBA mice, respectively, unpaired t -test, P = 0.047) was found in CBA mice after noise exposure.…”

Section: Resultsmentioning

confidence: 99%

Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice

Liu

Wang

et al. 2021

Front. Cell Dev. Biol.

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Noise exposure of a short period at a moderate level can produce permanent cochlear synaptopathy without seeing lasting changes in audiometric threshold. However, due to the species differences in inner hair cell (IHC) calcium current that we have recently discovered, the susceptibility to noise exposure may vary, thereby impact outcomes of noise exposure. In this study, we investigate the consequences of noise exposure in the two commonly used animal models in hearing research, CBA/CaJ (CBA) and C57BL/6J (B6) mice, focusing on the functional changes of cochlear IHCs. In the CBA mice, moderate noise exposure resulted in a typical fully recovered audiometric threshold but a reduced wave I amplitude of auditory brainstem responses. In contrast, both auditory brainstem response threshold and wave I amplitude fully recovered in B6 mice at 2 weeks after noise exposure. Confocal microscopy observations found that ribbon synapses of IHCs recovered in B6 mice but not in CBA mice. To further characterize the molecular mechanism underlying these different phenotypes in synaptopathy, we compared the ratio of Bax/Bcl-2 with the expression of cytochrome-C and found increased activity in CBA mice after noise exposure. Under whole-cell patch clamped IHCs, we acquired two-photon calcium imaging around the active zone to evaluate the Ca2+ clearance rate and found that CBA mice have a slower calcium clearance rate. Our results indicated that excessive accumulation of calcium due to acoustic overexposure and slow clearance around the presynaptic ribbon might lead to disruption of calcium homeostasis, followed by mitochondrial dysfunction of IHCs that cause susceptibility of noise-induced cochlear synaptopathy in CBA mice.

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The potential role of the SIRT1‐Nrf2 signaling pathway in alleviating hidden hearing loss via antioxidant stress

Zheng,

Zhang,

et al. 2024

Cell Biology International

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Hidden hearing loss (HHL) is characterized by normal audiometric thresholds but impaired auditory function, particularly in noisy environments. In vivo, we employed auditory brainstem response (ABR) testing and ribbon synapses counting to assess changes in mouse hearing function, and observed the morphology of hair cells through scanning electron microscopy. SRT1720 was administered to the cochlea via round window injection. In vitro, western blot analysis and RT‐qPCR were used, and Lenti‐shNrf2 was used to knockdown Nrf2 expression. In addition, various oxidative stress indicators were detected by immunofluorescence, kit‐based assays, and flow cytometry. ABR measurement of HHL mouse showed a significant increase in hearing threshold, as well as a decrease and delay in the I wave amplitude and latency on the first day after noise exposure. Histological observation showed a significant loss of ribbon synapses and stereocilia lodging. HHL mice exhibited oxidative stress, which was reduced by pretreatment with SRT1720. Additionally, SRT1720 could reduce hydrogen peroxide‐induced oxidative stress in HEI‐OC1 cells through activating the SIRT1/Nrf2 pathway. Subsequent experiments with Nrf2 knockdown confirmed the importance of this pathway. findings highlight oxidative stress as the primary contributor to HHL, with the SIRT1/Nrf2 signaling pathway emerging as a promising therapeutic target for alleviating HHL.

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Ginsenoside Rd Ameliorates Auditory Cortex Injury Associated With Military Aviation Noise-Induced Hearing Loss by Activating SIRT1/PGC-1α Signaling Pathway

Cited by 29 publications

References 49 publications

Protective Effect of Ginsenoside Rd on Military Aviation Noise-Induced Cochlear Hair Cell Damage

Protective Effect of Ginsenoside Rd on Military Aviation Noise-Induced Cochlear Hair Cell Damage

Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice

The potential role of the SIRT1‐Nrf2 signaling pathway in alleviating hidden hearing loss via antioxidant stress

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