The effectiveness of eugenol against cisplatin-induced ototoxicity

Introduction: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin. Objective: The aim of this study was to perform a b...

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Main Authors: Muhammed Sedat Sakat, Korhan Kilic, Fazile Nur Ekinci Akdemir, Serkan Yildirim, Gizem Eser, Ahmet Kiziltunc
Format: Article
Language:English
Published: Elsevier 2019-11-01
Series:Brazilian Journal of Otorhinolaryngology
Online Access:http://www.sciencedirect.com/science/article/pii/S1808869418302337
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author Muhammed Sedat Sakat
Korhan Kilic
Fazile Nur Ekinci Akdemir
Serkan Yildirim
Gizem Eser
Ahmet Kiziltunc
author_facet Muhammed Sedat Sakat
Korhan Kilic
Fazile Nur Ekinci Akdemir
Serkan Yildirim
Gizem Eser
Ahmet Kiziltunc
author_sort Muhammed Sedat Sakat
collection DOAJ
description Introduction: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin. Objective: The aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity. Methods: The study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15 mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100 mg/kg eugenol intraperitoneal for five consecutive days. 100 mg/kg eugenol was administered to cisplatin + eugenol group for 5 days. On the third day, these rats were received a single dose of 15 mg/kg cisplatin. The control group was given 8 mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24 h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations. Results: Cisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection. Conclusion: The study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters. Resumo: Introdução: A ototoxicidade refere-se ao dano celular ou comprometimento da função da orelha interna associado a qualquer agente terapêutico ou substância química e ainda representa o principal efeito colateral que restringe o uso da cisplatina. Objetivo: O objetivo deste estudo foi realizar uma investigação bioquímica, funcional e histopatológica do potencial efeito protetor do eugenol contra a ototoxicidade induzida pela cisplatina. Método: O estudo foi realizado com 24 ratos fêmeas Sprague Dawley. Testes de emissões otoacústicas por produto de distorção foram realizados em todos os animais, os quais foram randomizados em quatro grupos iguais. Uma única dose intraperitoneal de 15 mg/kg de cisplatina foi administrada ao grupo cisplatina, enquanto o grupo eugenol recebeu 100 mg/kg de eugenol intraperitoneal por cinco dias consecutivos. Foram administrados 100 mg/kg de eugenol ao grupo cisplatina + eugenol durante 5 dias. No terceiro dia, estes ratos receberam uma dose única de 15 mg/kg de cisplatina. O grupo controle recebeu 8 mL/kg/dia de solução salina intraperitoneal por cinco dias. O teste de emissões otoacústicas por produto de distorção foi repetido 24 horas após a administração final do medicamento. Todos os animais foram sacrificados e as cócleas foram posteriormente utilizadas para exames bioquímicos e histopatológicos. Resultados: A cisplatina causou estresse oxidativo na cóclea, prejudicou a estrutura coclear e reduziu significativamente os níveis da relação sinal/ruído. A administração de eugenol juntamente com a cisplatina reverteu esses efeitos e forneceu proteção funcional, bioquímica e histopatológica. Conclusão: Os achados do estudo representam a primeira indicação na literatura de que o eugenol pode proteger contra a ototoxicidade, eleva os níveis de enzimas antioxidantes e diminui os níveis dos parâmetros oxidantes. Keywords: Cisplatin-induced ototoxicity, Eugenol, DPOAE, Oxidative stress, 8-Hydroxy-2′-deoxyguanosine, Palavras-chave: Ototoxicidade induzida pela cisplatina, Eugenol, EOAPD, Estresse oxidativo, 8-Hidroxi-2′-deoxiguanosina
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spelling doaj.art-f0dcb4a5152948d8990d3f2efff8e5692022-12-21T19:46:05ZengElsevierBrazilian Journal of Otorhinolaryngology1808-86942019-11-01856766773The effectiveness of eugenol against cisplatin-induced ototoxicityMuhammed Sedat Sakat0Korhan Kilic1Fazile Nur Ekinci Akdemir2Serkan Yildirim3Gizem Eser4Ahmet Kiziltunc5Ataturk University, Faculty of Medicine, Department of Otorhinolaryngology, Erzurum, Turkey; Corresponding author.Ataturk University, Faculty of Medicine, Department of Otorhinolaryngology, Erzurum, TurkeyAgri Ibrahim Cecen University, High School of Health, Department of Nutrition and Dietetics, Agri, TurkeyAtaturk University, Faculty of Veterinary, Department of Pathology, Erzurum, TurkeyAtaturk University, Faculty of Veterinary, Department of Pathology, Erzurum, TurkeyAtaturk University, Faculty of Medicine, Department of Biochemistry, Erzurum, TurkeyIntroduction: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin. Objective: The aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity. Methods: The study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15 mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100 mg/kg eugenol intraperitoneal for five consecutive days. 100 mg/kg eugenol was administered to cisplatin + eugenol group for 5 days. On the third day, these rats were received a single dose of 15 mg/kg cisplatin. The control group was given 8 mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24 h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations. Results: Cisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection. Conclusion: The study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters. Resumo: Introdução: A ototoxicidade refere-se ao dano celular ou comprometimento da função da orelha interna associado a qualquer agente terapêutico ou substância química e ainda representa o principal efeito colateral que restringe o uso da cisplatina. Objetivo: O objetivo deste estudo foi realizar uma investigação bioquímica, funcional e histopatológica do potencial efeito protetor do eugenol contra a ototoxicidade induzida pela cisplatina. Método: O estudo foi realizado com 24 ratos fêmeas Sprague Dawley. Testes de emissões otoacústicas por produto de distorção foram realizados em todos os animais, os quais foram randomizados em quatro grupos iguais. Uma única dose intraperitoneal de 15 mg/kg de cisplatina foi administrada ao grupo cisplatina, enquanto o grupo eugenol recebeu 100 mg/kg de eugenol intraperitoneal por cinco dias consecutivos. Foram administrados 100 mg/kg de eugenol ao grupo cisplatina + eugenol durante 5 dias. No terceiro dia, estes ratos receberam uma dose única de 15 mg/kg de cisplatina. O grupo controle recebeu 8 mL/kg/dia de solução salina intraperitoneal por cinco dias. O teste de emissões otoacústicas por produto de distorção foi repetido 24 horas após a administração final do medicamento. Todos os animais foram sacrificados e as cócleas foram posteriormente utilizadas para exames bioquímicos e histopatológicos. Resultados: A cisplatina causou estresse oxidativo na cóclea, prejudicou a estrutura coclear e reduziu significativamente os níveis da relação sinal/ruído. A administração de eugenol juntamente com a cisplatina reverteu esses efeitos e forneceu proteção funcional, bioquímica e histopatológica. Conclusão: Os achados do estudo representam a primeira indicação na literatura de que o eugenol pode proteger contra a ototoxicidade, eleva os níveis de enzimas antioxidantes e diminui os níveis dos parâmetros oxidantes. Keywords: Cisplatin-induced ototoxicity, Eugenol, DPOAE, Oxidative stress, 8-Hydroxy-2′-deoxyguanosine, Palavras-chave: Ototoxicidade induzida pela cisplatina, Eugenol, EOAPD, Estresse oxidativo, 8-Hidroxi-2′-deoxiguanosinahttp://www.sciencedirect.com/science/article/pii/S1808869418302337
spellingShingle Muhammed Sedat Sakat
Korhan Kilic
Fazile Nur Ekinci Akdemir
Serkan Yildirim
Gizem Eser
Ahmet Kiziltunc
The effectiveness of eugenol against cisplatin-induced ototoxicity
Brazilian Journal of Otorhinolaryngology
title The effectiveness of eugenol against cisplatin-induced ototoxicity
title_full The effectiveness of eugenol against cisplatin-induced ototoxicity
title_fullStr The effectiveness of eugenol against cisplatin-induced ototoxicity
title_full_unstemmed The effectiveness of eugenol against cisplatin-induced ototoxicity
title_short The effectiveness of eugenol against cisplatin-induced ototoxicity
title_sort effectiveness of eugenol against cisplatin induced ototoxicity
url http://www.sciencedirect.com/science/article/pii/S1808869418302337
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