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Prevention of gentamicin ototoxicity with N-acetylcysteine and vitamin A

Published online by Cambridge University Press:  20 April 2016

I Aladag
Affiliation:
Department of Otorhinolaryngology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
M Guven
Affiliation:
Department of Otorhinolaryngology, Sakarya University Medical Faculty, Sakarya, Turkey
M Songu*
Affiliation:
Department of Otorhinolaryngology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
*
Address for correspondence: Assoc Prof Murat Songu, Department of Otorhinolaryngology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey Fax: +90 232 243 1530 E-mail: songumurat@yahoo.com

Abstract

Objective:

To investigate the use of systemic N-acetylcysteine and vitamin A in the prevention of gentamicin ototoxicity in rats.

Methods:

Forty-two Wistar rats were divided into four groups according to treatment: intratympanic saline, intratympanic gentamicin, intraperitoneal vitamin A after intratympanic gentamicin, and intraperitoneal N-acetylcysteine after intratympanic gentamicin. Signal-to-noise ratio and distortion product otoacoustic emissions were evaluated in all groups.

Results:

N-acetylcysteine had a significant protective effect at 1.5, 2, 3, 4, 6 and 8 kHz, whilst vitamin A had a significant protective effect at 2, 3, 4 and 6 kHz, as determined by the distortion product otoacoustic emission measurements. According to the signal-to-noise measurements, N-acetylcysteine had a significant protective effect at 1.5, 2, 3, 4, 6 and 8 kHz, whilst vitamin A had a significant protective effect at 3, 6 and 8 kHz.

Conclusion:

Gentamicin-induced hearing loss in rats may be prevented by the concomitant use of vitamin A and N-acetylcysteine. Specifically, N-acetylcysteine appeared to have a more protective effect than vitamin A for a greater range of noise frequencies.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2016 

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References

1 Ahmed, RM, Hannigan, IP, MacDougall, HG, Chan, RC, Halmagyi, GM. Gentamicin ototoxicity: a 23-year selected case series of 103 patients. Med J Aust 2012;196:701–4Google Scholar
2 Turnidge, JD, Waterston, JA. Gentamicin and ototoxicity: why this drug is still in use. Med J Aust 2012;196:665–6CrossRefGoogle Scholar
3 Kemp, DT. Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am 1978;64:1386–91CrossRefGoogle ScholarPubMed
4 Cohen-Kerem, R, Kisilevsky, V, Einarson, TR, Kozer, E, Koren, G, Rutka, JA. Intratympanic gentamicin for Ménière's disease: a meta-analysis. Laryngoscope 2004;114:2085–91CrossRefGoogle ScholarPubMed
5 Salt, AN, Gill, RM, Plontke, SK. Dependence of hearing changes on the dose of intratympanically applied gentamicin: a meta-analysis using mathematical simulations of clinical drug delivery protocols. Laryngoscope 2008;118:1793–800Google Scholar
6 Tepel, M. N-Acetylcysteine in the prevention of ototoxicity. Kidney Int 2007;72:231–2CrossRefGoogle ScholarPubMed
7 Khvoles, R, Freeman, S, Sohmer, H. Transient evoked otoacoustic emissions can be recorded in the rat. Hear Res 1996;97:120–6Google Scholar
8 Khvoles, R, Freeman, S, Sohmer, H. Development of transient evoked otoacoustic emissions in the neonatal rat. Audiol Neurootol 1998;3:4053 Google Scholar
9 Sockalingam, R, Freeman, S, Cherny, TL, Sohmer, H. Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals. Am J Otol 2000;21:521–7Google ScholarPubMed
10 Hatzopoulos, S, Di Stefano, M, Albertin, A, Martini, A. Evaluation of cisplatin ototoxicity in a rat animal model. Ann N Y Acad Sci 1999;884:211–25CrossRefGoogle Scholar
11 Saliba, I, El Fata, F, Ouelette, V, Robitaille, Y. Are intratympanic injections of N-acetylcysteine and methylprednisolone protective against cisplatin-induced ototoxicity? J Otolaryngol Head Neck Surg 2010;39:236–43Google ScholarPubMed
12 Kubow, S, Woodward, TL, Turner, JD, Nicodemo, A, Long, E, Zhao, X. Lipid peroxidation is associated with the inhibitory action of all-trans-retinoic acid on mammary cell transformation. Anticancer Res 2000;20:843–8Google Scholar
13 Ahn, JH, Kang, HH, Kim, YJ, Chung, JW. Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice. Biochem Biophys Res Commun 2005;335:485–90CrossRefGoogle ScholarPubMed
14 Boztepe, OF, Gün, T, Gür, ÖE, Karakuş, MF, Bilal, N, Arda, HN. Effect of N-acetylcysteine for the treatment of otitis media with effusion. J Med Updates 2014;4:20–4Google Scholar
15 Shim, HJ, Kang, HH, Ahn, JH, Chung, JW. Retinoic acid applied after noise exposure can recover the noise-induced hearing loss in mice. Acta Otolaryngol 2009;129:233–8Google Scholar
16 Muurling, T, Stankovic, KM. Metabolomic and network analysis of pharmacotherapies for sensorineural hearing loss. Otol Neurotol 2014;35:16 CrossRefGoogle ScholarPubMed
17 Emmett, SD, West, KP Jr. Gestational vitamin A deficiency: a novel cause of sensorineural hearing loss in the developing world? Med Hypotheses 2014;82:610 CrossRefGoogle ScholarPubMed
18 Hammer, Ø, Harper, DA, Ryan, PD. PAST: paleontological statistics software package for education and data analysis. Palaeontol Electron 2001;4:9 Google Scholar
19 Cheng, AG, Cunningham, LL, Rubel, EW. Mechanisms of hair cell death and protection. Curr Opin Otolaryngol Head Neck Surg 2005;13:343–8Google Scholar
20 Miman, MC, Ozturan, O, Iraz, M, Erdem, T, Olmez, E. Amikacin ototoxicity enhanced by Ginkgo biloba extract (EGb 761). Hear Res 2002;169:121–9Google Scholar
21 Feghali, JG, Liu, W, Van Der Water, TR. L-N-Acetyl-cysteine protection against cisplatin-induced auditory neuronal and hair cell toxicity. Laryngoscope 2001;111:1147–55CrossRefGoogle ScholarPubMed
22 Weinbroum, A, Rudick, V, Ben-Abraham, R, Karchevski, E. N-acetyl-L-cysteine for preventing lung reperfusion injury after liver ischemia-reperfusion: a possible dual protective mechanism in a dose-response study. Transplantation 2000;69:853–9Google Scholar
23 Mazzon, E, Britti, D, De Sarro, A, Caputi, AP, Cuzzocrea, S. Effect of N-acetylcysteine on gentamicin-mediated nephropathy in rats. Eur J Pharmacol 2001;424:7583 CrossRefGoogle ScholarPubMed
24 Damodaran, S, Parkin, KL, Fennema, OR, eds. Fennema's Food Chemistry, 4th edn. Boca Raton, Florida: CRC Press, 2008 Google Scholar
25 Lopez-Gonzalez, MA, Guerrero, JM, Rojas, F, Delgado, F. Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants. J Pineal Res 2000;28:7380 Google Scholar
26 Hyppolito, MA, de Oliveira, JA, Rossato, M, Holanda, F. Cisplatin ototoxicity and otoprotector to cilliated cells by ginkgo biloba extract: anatomic and electrophysiologic study [in Portuguese]. Rev Bras Otorrinolaringol 2003;69:504–11CrossRefGoogle Scholar
27 McAlpine, D, Johnstone, BM. The ototoxic mechanism of cisplatin. Hear Res 1990;47:191204 CrossRefGoogle ScholarPubMed