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      Combination of antioxidants and NFAT (nuclear factor of activated T cells) inhibitor protects auditory hair cells from ototoxic insult

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          Noise-induced hearing loss: a study on the pharmacological protection in the Sprague Dawley rat with N-acetyl-cysteine.

          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 emissions). The group which showed the best protection was that which received a total dosage of 1500 mg/kg of L-N-acetyl-cysteine. These data suggest that while L-Nacetyl-cysteine can partially protect the cochlea from continuous noise, the protection effect is strongly dose-dependent: lower dosages do not fully protect the cochlea and higher dosages can damage the rat systemically (e.g. pulmonary toxicity).
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            Preventing amikacin related ototoxicity with N-acetylcysteine in patients undergoing peritoneal dialysis.

            Amikacin is a frequently used antibiotic in the treatment of peritoneal dialysis (PD)-related peritonitis. Ototoxicity is a well-known complication of amikacin for which increased oxidative stress and free oxygen radicals are thought to be responsible. In this study, the effect of N-acetyl-cysteine (NAC) on cochlear function and oxidant situation in the amikacin related ototoxicity in PD-related peritonitis patients are investigated. Forty-six patients who had their first PD-related peritonitis attacks receiving empirical amikacin treatment were enrolled in the study. The patients were randomized into two groups; the first group (n = 23) as NAC receiving and the second group (n = 23) as a placebo receiving, control group. Otoacoustic emissions were measured before, 1 week after and 4 weeks after the treatment. Oxidative stress measurements were performed concurrently in order to evaluate the effectiveness of NAC. The results of screening with otoacoustic emission testing after amikacin treatment showed that cochlear function is protected especially in higher frequencies in NAC group when compared with the control group. Evaluation of the antioxidant status of the two groups showed no differences in the basal values, but at the first week there was an increase in the NAC group compared with the control group, and this increase became significant at the fourth week. NAC is found to be safe and effective in amikacin-related ototoxicity in patients with PD-related peritonitis. We suggest a close monitoring of the patients receiving amikacin containing treatment protocols and if amikacin is administrated supplementing the treatment with NAC.
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              Tissue culture of the organ of Corti

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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Journal of Neurochemistry
                J. Neurochem.
                Wiley
                0022-3042
                1471-4159
                September 2020
                December 15 2019
                September 2020
                : 154
                : 5
                : 519-529
                Affiliations
                [1 ]Department of Biomedicine University of Basel Basel Switzerland
                [2 ]Clinic for Otolaryngology, Head and Neck Surgery University Hospital Basel Basel Switzerland
                Article
                10.1111/jnc.14921
                f37199e6-d577-4a4f-b94d-b47cd53d9701
                © 2020

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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