Abstract
Free radicals and oxidative stress play an important role in the pathogenesis of noise-induced hearing loss (NIHL). Some ginseng monomers showed certain therapeutic effects in NIHL by scavenging free radicals. Therefore, we hypothesized that ginsenoside Rd (GSRd) may exert neuroprotective effects after noise-induced auditory system damage through a mechanism involving the SIRT1/PGC-1α signaling pathway. Forty-eight guinea pigs were randomly divided into four equal groups (normal control group, noise group, experimental group that received GSRd dissolved in glycerin through an intraperitoneal injection at a dose of 30 mg/kg body weight from 5 days before noise exposure until the end of the noise exposure period, and experimental control group). Hearing levels were examined by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Hematoxylin–eosin and Nissl staining were used to examine neuron morphology. RT-qPCR and western blotting analysis were used to examine SIRT1/PGC-1α signaling and apoptosis-related genes, including Bax and Bcl-2, in the auditory cortex. Bax and Bcl-2 expression was assessed via immunohistochemistry analysis. Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were determined using a commercial testing kit. Noise exposure was found to up-regulate ABR threshold and down-regulate DPOAE amplitudes, with prominent morphologic changes and apoptosis of the auditory cortex neurons (p < 0.01). GSRd treatment restored hearing loss and remarkably alleviated morphological changes or apoptosis (p < 0.01), concomitantly increasing Bcl-2 expression and decreasing Bax expression (p < 0.05). Moreover, GSRd increased SOD and GSH-Px levels and decreased MDA levels, which alleviated oxidative stress damage and activated SIRT1/PGC-1α signaling pathway. Taken together, our findings suggest that GSRd ameliorates auditory cortex injury associated with military aviation NIHL by activating the SIRT1/PGC-1α signaling pathway, which can be an attractive pharmacological target for the development of novel drugs for NIHL treatment.
Highlights
Noise, such as traffic noise, industrial noise, construction noise, and living noise, is a factor that seriously endangers people’s health, especially through serious auditory system damage that may result in noiseinduced hearing loss (NIHL)
Microarray dataset GSE39551 was obtained from the Gene Expression Omnibus (GEO) database to explore gene expression profiles after silent information regulator 1 (SIRT1) activation
The results of this study showed that ginsenoside Rd (GSRd) significantly ameliorates auditory cortex injury associated with military aviation NIHL in guinea pigs by activating the SIRT1/proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway (Figure 7)
Summary
Noise, such as traffic noise, industrial noise, construction noise, and living noise, is a factor that seriously endangers people’s health, especially through serious auditory system damage that may result in NIHL. The most common preventive measure against NIHL is wearing hearing protection devices. The aviation unit ground crew is often unable or unwilling to wear these devices, including earplugs, due to poor compliance and comfort. Their auditory systems are vulnerable to noise damage and they have a high prevalence of hearing system diseases, such as NIHL, tinnitus, and auditory allergy (Miao et al, 2019). Research on supplements for hearing protection devices that would provide a comprehensive protection and reduce the incidence of NIHL and other diseases in personnel working in a noisy environment, especially helicopter units and ground service personnel, is mandatory
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