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Comparison of the protective effects of intratympanic dexamethasone and methylprednisolone against cisplatin-induced ototoxicity

Published online by Cambridge University Press:  02 February 2016

H E Özel*
Affiliation:
Department of Otolaryngology, Kocaeli Derince Research and Training Hospital, Kocaeli, Turkey
F Özdoğan
Affiliation:
Department of Otolaryngology, Kocaeli Derince Research and Training Hospital, Kocaeli, Turkey
S G Gürgen
Affiliation:
Department of Histology and Embryology, Celal Bayar University School of Vocational Health Service, Manisa, Turkey
E Esen
Affiliation:
Department of Otolaryngology, Kocaeli Derince Research and Training Hospital, Kocaeli, Turkey
S Genç
Affiliation:
Department of Otolaryngology, Kocaeli Derince Research and Training Hospital, Kocaeli, Turkey
A Selçuk
Affiliation:
Department of Otolaryngology, Kocaeli Derince Research and Training Hospital, Kocaeli, Turkey
*
Address for correspondence: Dr H E Özel, Kulak Burun Boğaz Kliniği, Kocaeli Derince Eğitim ve Araştırma Hastanesi, 41900 Kocaeli, Turkey Fax: +90 262 2335536 E-mail: drsgenc@yahoo.com

Abstract

Objective:

This study aimed to compare the efficacies of intratympanic dexamethasone and methylprednisolone in preventing in cisplatin-induced ototoxicity in rats.

Methods:

Experimental groups of rats (n = 8 each) received intratympanic isotonic saline, intraperitoneal cisplatin and intratympanic isotonic saline, intraperitoneal cisplatin and intratympanic dexamethasone, or intraperitoneal cisplatin and intratympanic methylprednisolone. Distortion product otoacoustic emission thresholds were compared on days 0 and 10 in all rats, and correlations between drug effects and changes in cochlear histology were evaluated.

Results:

Distortion product otoacoustic emission thresholds were comparable in groups III and IV (p > 0.05). Significant protection against cisplatin-induced ototoxicity was seen in groups III and IV compared with group II (p < 0.05). Dexamethasone and, to a lesser extent, methylprednisolone protected against cellular apoptosis in cisplatin-induced ototoxicity.

Conclusion:

Dexamethasone (and possibly methylprednisolone) may be clinically useful as an intratympanic chemopreventive agent to treat cisplatin ototoxicity. Future clinical studies should investigate the use of dexamethasone for this purpose in adult patients.

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

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References

1Rybak, LP, Whitworth, CA, Mukherjea, D, Ramkumar, V. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear Res 2007;226:157–67CrossRefGoogle ScholarPubMed
2Rybak, LP, Mukherjea, D, Jajoo, S, Ramkumar, V. Cisplatin ototoxicity and protection: clinical and experimental studies. Tohoku J Exp Med 2009;219:177–86CrossRefGoogle ScholarPubMed
3Hellberg, V, Wallin, I, Ehrsson, H, Laurell, G. Cochlear pharmacokinetics of cisplatin: an in vivo study in the guinea pig. Laryngoscope 2013;123:3172–7CrossRefGoogle Scholar
4Calli, C, Pinar, E, Oncel, S, Alper Bagriyanik, H, Umut Sakarya, E. Recovery of hearing in cisplatin-induced ototoxicity in the guinea pig with intratympanic dexamethasone. Indian J Otolaryngol Head Neck Surg 2012;64:4650CrossRefGoogle ScholarPubMed
5Daldal, A, Odabasi, O, Serbetcioglu, B. The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs. Otolaryngol Head Neck Surg 2007;137:747–52CrossRefGoogle ScholarPubMed
6Laurell, G, Borg, E. Ototoxicity of cisplatin in gynaecological cancer patients. Scand Audiol 1988;17:241–7CrossRefGoogle ScholarPubMed
7Guide for the Care and Use of Laboratory Animals, 8th edn. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Washington, DC: National Academies Press (US), 2011Google Scholar
8Gross, D, Tolba, RH. Ethics in animal-based research. Eur Surg Res 2015;55:4357CrossRefGoogle ScholarPubMed
9Saliba, 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
10Saliba, I, El Fata, F. Is intratympanic injection of erdosteine protective against cisplatin-induced ototoxicity? Neurotox Res 2012;21:302–8CrossRefGoogle ScholarPubMed
11Munguia, R, Sahmkow, SI, Funnell, WR, Daniel, SJ. Transtympanic Ringer's lactate application in the prevention of cisplatinum-induced ototoxicity in a chinchilla animal model. Otolaryngol Head Neck Surg 2010;143:134–40CrossRefGoogle Scholar
12Celebi, S, Gurdal, MM, Ozkul, MH, Yasar, H, Balikci, HH. The effect of intratympanic vitamin C administration on cisplatin-induced ototoxicity. Eur Arch Otorhinolaryngol 2013;270:1293–7CrossRefGoogle ScholarPubMed
13Riga, MG, Chelis, L, Kakolyris, S, Papadopoulos, S, Stathakidou, S, Chamalidou, E et al. Transtympanic injections of N-acetylcysteine for the prevention of cisplatin-induced ototoxicity: a feasible method with promising efficacy. Am J Clin Oncol 2013;36:16CrossRefGoogle ScholarPubMed
14Topdag, M, Iseri, M, Gelenli, E, Yardimoglu, M, Yazir, Y, Ulubil, SA et al. Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity. J Laryngol Otol 2012;126:1091–6CrossRefGoogle ScholarPubMed
15Paksoy, M, Ayduran, E, Sanlı, A, Eken, M, Aydın, S, Oktay, ZA. The protective effects of intratympanic dexamethasone and vitamin E on cisplatin-induced ototoxicity are demonstrated in rats. Med Oncol 2011;28:615–21CrossRefGoogle ScholarPubMed
16Hill, GW, Morest, DK, Parham, K. Cisplatin-induced ototoxicity: effect of intratympanic dexamethasone injections. Otol Neurotol 2008;29:1005–11CrossRefGoogle ScholarPubMed
17Murphy, D, Daniel, SJ. Intratympanic dexamethasone to prevent cisplatin ototoxicity: a guinea pig model. Otolaryngol Head Neck Surg 2011;145:452–7CrossRefGoogle ScholarPubMed
18Hughes, AL, Hussain, N, Pafford, R, Parham, K. Dexamethasone otoprotection in a multidose cisplatin ototoxicity mouse model. Otolaryngol Head Neck Surg 2014;150:115–20CrossRefGoogle Scholar
19Kim, HJ, Lee, JH, Kim, SJ, Oh, GS, Moon, HD, Kwon, KB et al. Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity. J Neurosci 2010;30:3933–46CrossRefGoogle ScholarPubMed
20Kolls, J, Xie, J, LeBlanc, R, Malinski, T, Nelson, S, Summer, W et al. Rapid induction of messenger RNA for nitric oxide synthase II in rat neutrophils in vivo by endotoxin and its suppression by prednisolone. Proc Soc Exp Biol Med 1994;205:220–9CrossRefGoogle ScholarPubMed
21Nagura, M, Iwasaki, S, Wu, R, Mizuta, K, Umemura, K, Hoshino, T. Effects of corticosteroid, contrast medium and ATP on focal microcirculatory disorders of the cochlea. Eur J Pharmacol 1999;366:4753CrossRefGoogle ScholarPubMed
22Herr, I, Ucur, E, Herzer, K, Okouoyo, S, Ridder, R, Krammer, PH et al. Glucocorticoid cotreatment induces apoptosis resistance toward cancer therapy in carcinomas. Cancer Res 2003;63:3112–20Google ScholarPubMed
23Marshak, T, Steiner, M, Kaminer, M, Levy, L, Shupak, A. Prevention of cisplatin-induced hearing loss by intratympanic dexamethasone: a randomized controlled study. Otolaryngol Head Neck Surg 2014;150:983–90CrossRefGoogle ScholarPubMed
24Parham, K. Can intratympanic dexamethasone protect against cisplatin ototoxicity in mice with age-related hearing loss? Otolaryngol Head Neck Surg 2011;145:635–40CrossRefGoogle ScholarPubMed