Role of glutathione in protection against noise-induced hearing loss (original) (raw)
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Glutathione limits noise-induced hearing loss
Hearing Research, 2000
The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying noise-induced hearing loss (NIHL). Glutathione (GSH) is an important cellular antioxidant that limits cell damage by ROS. In this study, we investigated the effectiveness of a GSH supplement to protect GSH-deficient animals from NIHL. Pigmented guinea pigs were exposed to a 4 kHz octave band noise, 115 dB SPL, for 5 h. Group 1 had a normal diet, while groups 2, 3 and 4 were fed a 7% low protein diet (leading to lowered tissue levels of GSH) for 10 days prior to noise exposure. One hour before, immediately after and 5 h after noise exposure, subjects received either an intraperitoneal injection of 5 ml/kg body weight of 0.9% NaCl (groups 1 and 2), 0.4 M glutathione monoethyl ester (GSHE; group 3) or 0.8 M GSHE (group 4). Auditory thresholds were measured by evoked brain stem response at 2, 4, 8, 12, 16 and 20 kHz before and after noise exposure. Ten days post exposure, group 1 showed noise-induced threshold shifts of approximately 20 dB at 2, 16 and 20 kHz and 35 to 40 dB at other frequencies. Threshold shifts in group 2 were significantly greater than baseline at 2, 4, 16 and 20 kHz. GSHE supplementation in a dose-dependent fashion attenuated the threshold shifts in the low protein diet animals. Hair cell loss, as evaluated with cytocochleograms, was consistent with the auditory-evoked brainstem response results. Group 2 exhibited significantly more hair cell loss than any of the other groups; hair cell loss in group 3 was similar to that seen in group 1; group 4 showed less loss than group 1. These results indicate that GSH is a significant factor in limiting noiseinduced cochlear damage. This is compatible with the notion that ROS generation plays a role in NIHL and that antioxidant treatment may be an effective prophylactic intervention.
Acta otorhinolaryngologica Italica : organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale, 2006
Noise-induced hearing loss is one of the most common causes of deafness and, at present, there is no treatment for the recovery of the normal hearing threshold after prolonged exposure to loud acoustic stimuli and the generation of acoustic trauma. Prolonged exposure to noise can cause oxidative stress in the cochlea which results in the loss (via apoptotic pathways) of the outer hair cells of the organ of Corti. It has been demonstrated that some antioxidant molecules, for example L-N-acetyl-cysteine, can prevent oxidative stress in the inner ear. Aim of the study was to evaluate whether L-N-acetyl-cysteine, given at various dosages, can preserve the fine structures of the cochlea from the insult of continuous noise. A series of 18 Sprague Dawley male albino rats were exposed to continuous noise (8 kHz octave band noise, 105 dB SPL, 4 hours), and cochlear functionality was evaluated by recordings of transient evoked otoacoustic emissions and distortion products otoacoustic emission...
Journal of Neuroscience, 2013
This study addresses the relationship between cochlear oxidative damage and auditory cortical injury in a rat model of repeated noise exposure. To test the effect of increased antioxidant defenses, a water-soluble coenzyme Q 10 analog (Q ter ) was used. We analyzed auditory function, cochlear oxidative stress, morphological alterations in auditory cortices and cochlear structures, and levels of coenzymes Q 9 and Q 10 (CoQ 9 and CoQ 10 , respectively) as indicators of endogenous antioxidant capability. We report three main results. First, hearing loss and damage in hair cells and spiral ganglion was determined by noise-induced oxidative stress. Second, the acoustic trauma altered dendritic morphology and decreased spine number of II-III and V-VI layer pyramidal neurons of auditory cortices. Third, the systemic administration of the water-soluble CoQ 10 analog reduced oxidative-induced cochlear damage, hearing loss, and cortical dendritic injury. Furthermore, cochlear levels of CoQ 9 and CoQ 10 content increased. These findings indicate that antioxidant treatment restores auditory cortical neuronal morphology and hearing function by reducing the noise-induced redox imbalance in the cochlea and the deafferentation effects upstream the acoustic pathway.
Oxidative stress pathways in the potentiation of noise-induced hearing loss by acrylonitrile
Hearing Research, 2007
We hypothesize that the disruption of antioxidant defenses is a key mechanism whereby chemical contaminants can potentiate noise-induced hearing loss (NIHL). This hypothesis was tested using acrylonitrile (ACN), a widely used industrial chemical whose metabolism is associated with glutathione (GSH) depletion and cyanide (CN) generation. CN, in turn, can inhibit Cu/Zn superoxide dismutase (SOD). We have shown previously that ACN potentiates NIHL, even with noise exposure approaching permissible occupational levels. However, the relative involvement of GSH depletion and/or CN production in this potentiation is still unknown. In this study, we altered these metabolic pathways pharmacologically in order to further delineate the role of specific antioxidants in the protection of the cochlea. We investigated the effects of sodium thiosulfate (STS), a CN inhibitor, 4-methylpyrazole (4MP), a drug that blocks CN generation by competing with CYP2E1, and L-N-acetylcysteine (L-NAC), a pro-GSH drug, in order to distinguish between GSH depletion and CN production as the mechanism responsible for potentiation of NIHL by ACN. Long-Evans rats were exposed to an octave-band noise (97 dB SPL, 4 h/day, 5 days) and ACN (50 mg/kg). Separate pre-treatments with STS (150 mg/kg), 4MP (100 mg/kg) and L-NAC (4 · 400 mg/kg) all dramatically reduced blood CN levels, but only L-NAC significantly protected GSH levels in both the liver and the cochlea. Concurrently, only L-NAC treatment decreased the auditory loss and hair cell loss resulting from ACN + noise, suggesting that GSH is involved in the protection of the cochlea against reactive oxygen species generated by moderate noise levels. On the other hand, CN does not seem to be involved in this potentiation. Published by Elsevier B.V.
Cochlear Mechanisms in Noise Induced Hearing Loss
Medicine Science | International Medical Journal, 2015
Glucocorticoid (Gc) is a steroid hormone secreted from the adrenal cortex in response to stress, which acts by binding to cytoplasmic glucocorticoid receptors (GRs). Dexamethasone (DeX) is a synthetic GC exhibiting immunosuppressive effects in both human and rodent models of hearing loss. While clinical evidence has shown the effectiveness of DEX for treatment of various inner ear diseases, its mechanisms of action and the optimal timing of treatment are not well understood. in the present study, intergroup comparisons were conducted based on the time point of treatment with DEX: (1) pretreatment; (2) posttreatment; and (3) pre&post-noise. The pre&post DEX treatment group showed a significant improvement in threshold shift at 1 day post-noise exposure as compared to the TTS (transient threshold shift)-only group at 8 and 16 kHz. Both TTS and PTS (permanent threshold shift) significantly reduced cochlear GR mRNA expression and increased serum corticosterone and cochlear inflammatory cytokines. The pre&post DEX treatment group showed a significant decrease in serum corticosterone level as compared to other DEX treatment groups and TTS-treated group at 3 days after acoustic trauma. Our results suggest that the timing of DEX administration differentially modulates systemic steroid levels, GR expression and cochlear cytokine expression. Glucocorticoids (GCs) are a class of steroid hormones secreted from the adrenal cortex in response to stress, which protect the organism against the negative effects of that stress 1-4. They are among the most commonly prescribed drugs and are used for a wide range of medical conditions, including inner ear diseases, e.g., sudden idiopathic hearing loss 5 , acute noise-induced hearing loss 6 , and Ménière's disease 7. GCs exert powerful antiinflammatory effects by inhibiting several inflammatory mediators and increasing cochlear blood flow, to prevent hair cell damage caused by inflammation and ischemia in the inner ear 8-12. The actions of GCs are predominantly mediated through glucocorticoid receptors (GRs). GRs are ubiquitously expressed throughout the body, including the inner ear. In rodents, GRs are highly expressed in the stria vascularis, inner hair cells, outer hair cells (OHCs), and spiral ligament of the cochlea and cochlear nerve 13,14. In humans, the highest level of GR expression is found in the spiral ligament, with the lowest level seen in the saccule 15. Hearing function has been reported to be closely related to GR expression 11,15-19. Dexamethasone (DEX), a synthetic GC, is widely used clinically due to its antiinflammatory, antishock, and immunosuppressive properties. As shown in our previous studies and confirmed by other groups, systemic or
Acta Oto-laryngologica, 2010
Conclusion: Changes in the metabolism of arachidonic acid (AA) might be part of a noise-induced compensatory mechanism with regional specificity. Objectives: The released imbalance of prostaglandins and leukotrienes, both AA metabolites, might result in altered blood flow regulation in the inner ear and probably contributes to noise-induced hearing loss. The aim of this study was to gain further information about noise-dependent changes in AA metabolism in the mammalian cochlea. Methods: In this prospective animal study, 10 male guinea pigs were exposed to tone bursts for 1 h at 70 dB sound pressure level (SPL) (n = 5) or 90 dB SPL (n = 5). Five animals were used as controls. Alterations in cyclooxygenase 1 (COX-1) and 5-lipoxygenase (5-LO) expression were determined by quantitative immunohistochemical analysis in 11 cochlear regions. Results: COX-1 expression was decreased after both 70 dB SPL and 90 dB SPL exposure in most cell types of the organ of Corti and increased in the nerve fibers of the osseous spiral lamina. 5-LO was lowered after 90 dB SPL exposure, preferentially in the third cochlear turn in the organ of Corti, in the first and second turn in spiral ganglion cells, and in all turns in the stria vascularis.
Molecular Biology Reports
Noise can change the pattern of gene expression inducing sensorineural hearing impairment. There is no investigation on effects of noise frequency on the expression of GJB2 and SLC26A4 genes involved in congenital hearing impairment in cochlear tissue. This study investigated impacts of white and purple noise on gene expression and pathologic changes of cochlear tissue. In this study, 32 adult male Westar rats were selected and divided into experimental groups WN (animals exposed to white noise with a frequency range of 100-20000 Hz), PN (animals exposed to purple noise with a frequency range of 4-20 kHz) and control groups. All experimental groups were exposed to a sound pressure level of 118-120 dB for 8 hours per day. Cochlear tissue sampling was performed for tissue pathology studies, also RNA was extracted at 1 hour & 1 week after cessation of noise exposure. The results showed that Both white and purple noises caused permanent damage to the cortical, estrosilica systems of hair cells and ganglion of the hearing nerve. GJB2 and SLC26A4 were downregulated in both groups exposed with white and purple noise. However, differences are notably more signi cant in 1 weak post-exposure than 1 hour. Our Findings suggest GJB2 and SLC26A4 can be considered as biomarkers of response to noise frequency which is associated with the pathological response of cochlear tissue, leading to sensorineural hearing impairment. It would be suggested the demand for a more conventional approach to assessment of noise-induced hearing loss and subsequently the practice of hearing protection programs.
Protective effects of N-acetylcysteine on noise-induced hearing loss in guinea pigs
Acta otorhinolaryngologica Italica : organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale, 2009
Increasing evidence suggests the involvement of oxidative stress in noise-induced hearing loss. The present study analysed, in an animal experimental model, the time course of the pathogenic mechanisms of noise-induced cochlear damage and the efficacy of the antioxidant drug N-acetylcysteine in reducing noise ototoxicity. Animals were divided into two groups, exposed to noise one treated with N-acetylcysteine for 3 days and one (the control group) with saline. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 minutes. Electrocochleographic recordings were made from an implanted round window electrode and the compound action potentials were measured daily at 2-16 kHz for 7 days. Morphological changes were analysed by scanning electron microscopy. The acoustic threshold measured 1 hour after acoustic trauma was elevated in the control group to 70-90 dB in the higher frequencies of the compound action potential audiogram, with a maximum threshold elev...