Otoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatina
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/3444 |
Resumo: | This paper aimed to investigate the apoptosis modulation pathway and the otoprotection mechanism of N-acetylcysteine (NAC) through the analysis of the glutathione peroxidase (GSH-Px) enzyme and the Bcl-2 protein expression in outer hair cells (OHCs) of rats treated with cisplatin. The listening function was also assessed in mice under the effect of different doses of cisplatin and NAC. Two experiments were performed, named A and B, the first being over an experimental period of five days, and the second during three days. Each experiment comprised four groups, under the following protocols: group A1 (negative control): intraperitoneally saline solution 0,9%, in the same volume corresponding to cisplatin dose; group A2 (positive control): 100mg/kg/day of NAC, oral administration by gavage; group A3 (ototoxic): 3mg/kg/day of intraperitoneally cisplatin; group A4 (ototoxic with otoprotection): 100 mg/kg/day of NAC oral administration by gavage, one hour before the administration of 3 mg/kg/day of intraperitoneally cisplatin; group B1 (negative control): intraperitoneally saline solution 0,9% in the same volume corresponding to the cisplatin dose (8mg/kg/day); group B2 (positive control): 300 mg/kg/day of NAC, oral administration by gavage; group B3 (ototoxic): 8 mg/kg/day of intraperitoneally cisplatin; group B4 (ototoxic with otoprotection): 300 mg/kg/day of NAC orally by gavage, one hour before the administration of 8 mg/Kg/day of intraperitoneally cisplatin. The animals in experiment A underwent otoscopy, distortion-product otoacustic emissions (DPOAEs) and brainstem auditory evoked potential (BAEP), before and after the administration of drugs. The animals in experiment B underwent the same testing in pre- and post-treatment, their tympanic bulla being removed ant their cochleae prepared for anatomical assessment with scanning electron microscopy and immunofluorescence for labeling the GSH-Px enzyme and the Bcl-2 protein. In experiment A, it was verified that there was no significant decrease in the signal-to-noise ratio of DPOEAs, but there was a significant increase in the electrophysiologic threshold obtained through BAEP in groups A3 e A4. In experiment B, it was verified that: there was no significant increase in the electrophysiologic threshold obtained through BAEP; the OHCs remained anatomically intact; the GSH-Px enzyme showed immunostaining absent in group B1 and immunostaining present in groups B2, B3 and B4; the Bcl-2 protein showed immunostaining absent in all groups. From the results, it was concluded that the listening function was more impaired by the exposure to a subdose of cisplatin over a longer period, the apoptosis modulation pathway in outer hair cells of mice treated with cisplatin is related to the expression of the GSH-Px enzyme and not expression of the Bcl-2 protein. |
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2016-03-012016-03-012015-03-10GONÇALVES, Maiara Santos. Otoprotection by N-acetylcysteine and the apoptosis modulation pathway in hair cells of rats treated with cisplatin. 2015. 124 f. Tese (Doutorado em Fonoaudiologia) - Universidade Federal de Santa Maria, Santa Maria, 2015.http://repositorio.ufsm.br/handle/1/3444This paper aimed to investigate the apoptosis modulation pathway and the otoprotection mechanism of N-acetylcysteine (NAC) through the analysis of the glutathione peroxidase (GSH-Px) enzyme and the Bcl-2 protein expression in outer hair cells (OHCs) of rats treated with cisplatin. The listening function was also assessed in mice under the effect of different doses of cisplatin and NAC. Two experiments were performed, named A and B, the first being over an experimental period of five days, and the second during three days. Each experiment comprised four groups, under the following protocols: group A1 (negative control): intraperitoneally saline solution 0,9%, in the same volume corresponding to cisplatin dose; group A2 (positive control): 100mg/kg/day of NAC, oral administration by gavage; group A3 (ototoxic): 3mg/kg/day of intraperitoneally cisplatin; group A4 (ototoxic with otoprotection): 100 mg/kg/day of NAC oral administration by gavage, one hour before the administration of 3 mg/kg/day of intraperitoneally cisplatin; group B1 (negative control): intraperitoneally saline solution 0,9% in the same volume corresponding to the cisplatin dose (8mg/kg/day); group B2 (positive control): 300 mg/kg/day of NAC, oral administration by gavage; group B3 (ototoxic): 8 mg/kg/day of intraperitoneally cisplatin; group B4 (ototoxic with otoprotection): 300 mg/kg/day of NAC orally by gavage, one hour before the administration of 8 mg/Kg/day of intraperitoneally cisplatin. The animals in experiment A underwent otoscopy, distortion-product otoacustic emissions (DPOAEs) and brainstem auditory evoked potential (BAEP), before and after the administration of drugs. The animals in experiment B underwent the same testing in pre- and post-treatment, their tympanic bulla being removed ant their cochleae prepared for anatomical assessment with scanning electron microscopy and immunofluorescence for labeling the GSH-Px enzyme and the Bcl-2 protein. In experiment A, it was verified that there was no significant decrease in the signal-to-noise ratio of DPOEAs, but there was a significant increase in the electrophysiologic threshold obtained through BAEP in groups A3 e A4. In experiment B, it was verified that: there was no significant increase in the electrophysiologic threshold obtained through BAEP; the OHCs remained anatomically intact; the GSH-Px enzyme showed immunostaining absent in group B1 and immunostaining present in groups B2, B3 and B4; the Bcl-2 protein showed immunostaining absent in all groups. From the results, it was concluded that the listening function was more impaired by the exposure to a subdose of cisplatin over a longer period, the apoptosis modulation pathway in outer hair cells of mice treated with cisplatin is related to the expression of the GSH-Px enzyme and not expression of the Bcl-2 protein.Este trabalho teve o objetivo de investigar o mecanismo de otoproteção da N-acetilcisteína (NAC) e a via de modulação da apoptose por meio da análise da expressão da enzima glutationa peroxidase (GSH-Px) e da proteína Bcl-2 em células ciliadas externas (CCEs) de ratos tratados com cisplatina. Também foi avaliada a função auditiva de ratos sob efeito de diferentes doses de cisplatina e NAC. Foram realizados dois experimentos, denominados de A e B, sendo o primeiro com um período experimental de cinco dias e o segundo de três dias. Cada experimento foi composto por quatro grupos, submetidos aos seguintes protocolos: grupo A1 (controle negativo): solução fisiológica 0,9%, via intraperitoneal, no mesmo volume correspondente à dose de cisplatina; grupo A2 (controle positivo): 100mg/Kg/dia de NAC, via oral por gavagem; grupo A3 (ototóxico): 3mg/Kg/dia de cisplatina via intraperitoneal; grupo A4 (ototóxico com otoproteção): 100 mg/Kg/dia de NAC via oral por gavagem, uma hora antes da administração de 3 mg/Kg/dia de cisplatina via intraperitoneal; grupo B1 (controle negativo): solução fisiológica 0,9% via intraperitoneal no mesmo volume correspondente à dose de cisplatina (8mg/Kg/dia); grupo B2 (controle positivo): 300 mg/Kg/dia de NAC via oral por gavagem; grupo B3 (ototóxico): 8 mg/Kg/dia de cisplatina via intraperitoneal; grupo B4 (ototóxico com otoproteção): 300 mg/Kg/dia de NAC via oral por gavagem, uma hora antes da administração via intraperitoneal de 8 mg/Kg/dia de cisplatina. Os animais do experimento A realizaram otoscopia, emissões otoacústicas produto de distorção (EOAPD) e potencial evocado auditivo de tronco encefálico (PEATE), antes e depois da administração das drogas. Os animais do experimento B realizaram estas mesmas avaliações também no pré e pós-tratamento, além de terem suas bulas timpânicas removidas e suas cócleas preparadas para a avaliação anatômica com microscopia eletrônica de varredura e imunofluorescência para a marcação da enzima GSH-Px e da proteína Bcl-2. No experimento A, verificou-se que não houve diminuição significativa da relação sinal-ruído das EOAPD, porém houve aumento significativo do limiar eletrofisiológico obtido por PEATE nos grupos A3 e A4. No experimento B, verificou-se que: não houve aumento significativo do limiar eletrofisiológico obtido por PEATE; as CCEs mantiveram-se anatomicamente íntegras; a enzima GSH-Px apresentou imunomarcação ausente no grupo B1 e imunomarcação presente nos grupos B2, B3 e B4; a proteína Bcl-2 apresentou imunomarcação ausente em todos os grupos estudados. A partir dos resultados, concluiu-se que a função auditiva foi mais prejudicada com a exposição de uma subdose de cisplatina durante um período mais prolongado, a via de modulação da apoptose nas células ciliadas externas de ratos tratados com cisplatina está relacionada com a expressão da enzima GSH-Px e não expressão da proteína Bcl-2.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Distúrbios da Comunicação HumanaUFSMBRFonoaudiologiaCisplatinaRadicais livresEstresse oxidativoApoptoseOtoproteçãoCócleaCisplatinFree radicalsOxidative stressApoptosisOtoprotectionCochleaCNPQ::CIENCIAS DA SAUDE::FONOAUDIOLOGIAOtoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatinaOtoprotection by N-acetylcysteine and the apoptosis modulation pathway in hair cells of rats treated with cisplatininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisSilveira, Aron Ferreira dahttp://lattes.cnpq.br/0131332430440217Hyppolito, Miguel Angelohttp://lattes.cnpq.br/5535637780238796Piccoli, Jacqueline da Costa Escobarhttp://lattes.cnpq.br/5099227329574183Cruz, Ivana Beatrice Mânica dahttp://lattes.cnpq.br/3426369324110716Biaggio, Eliara Pinto Vieirahttp://lattes.cnpq.br/6091731551273820Santos Filha, Valdete Alves Valentins doshttp://lattes.cnpq.br/3042191385044226http://lattes.cnpq.br/0016903220423615Gonçalves, Maiara Santos400700000003400300500300300300300300dcee4d36-cc5e-4e87-84dd-90217cc40046f24f6d0a-76a4-4a45-9171-a9ccd5067b639337278b-9b38-4de3-8b71-8b05ecb4cd7f0357d6e0-7f30-40b8-a6b2-4bd929a601153e70f8d1-28e2-435e-ae3a-51a0a48a38cd6e997364-d4fa-4b43-83b3-4ef8897b678e2bf39d2e-5916-402a-9f0e-d2f325a295ddinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALGONCALVES, MAIARA SANTOS.pdfapplication/pdf3246769http://repositorio.ufsm.br/bitstream/1/3444/1/GONCALVES%2c%20MAIARA%20SANTOS.pdfe097c64177673809dfeabb67b1e0c0e7MD51TEXTGONCALVES, MAIARA SANTOS.pdf.txtGONCALVES, MAIARA SANTOS.pdf.txtExtracted texttext/plain195146http://repositorio.ufsm.br/bitstream/1/3444/2/GONCALVES%2c%20MAIARA%20SANTOS.pdf.txt06e9eb784a926449d5b3f443f4950d02MD52THUMBNAILGONCALVES, MAIARA SANTOS.pdf.jpgGONCALVES, MAIARA SANTOS.pdf.jpgIM Thumbnailimage/jpeg4970http://repositorio.ufsm.br/bitstream/1/3444/3/GONCALVES%2c%20MAIARA%20SANTOS.pdf.jpg331fb77a0fcaf0d3741830b909796a19MD531/34442022-09-02 10:43:02.115oai:repositorio.ufsm.br:1/3444Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-09-02T13:43:02Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Otoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatina |
dc.title.alternative.eng.fl_str_mv |
Otoprotection by N-acetylcysteine and the apoptosis modulation pathway in hair cells of rats treated with cisplatin |
title |
Otoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatina |
spellingShingle |
Otoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatina Gonçalves, Maiara Santos Cisplatina Radicais livres Estresse oxidativo Apoptose Otoproteção Cóclea Cisplatin Free radicals Oxidative stress Apoptosis Otoprotection Cochlea CNPQ::CIENCIAS DA SAUDE::FONOAUDIOLOGIA |
title_short |
Otoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatina |
title_full |
Otoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatina |
title_fullStr |
Otoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatina |
title_full_unstemmed |
Otoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatina |
title_sort |
Otoproteção da N-acetilcisteína e via de modulação da apoptose em células ciliadas de ratos tratados com cisplatina |
author |
Gonçalves, Maiara Santos |
author_facet |
Gonçalves, Maiara Santos |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Silveira, Aron Ferreira da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0131332430440217 |
dc.contributor.advisor-co1.fl_str_mv |
Hyppolito, Miguel Angelo |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/5535637780238796 |
dc.contributor.referee1.fl_str_mv |
Piccoli, Jacqueline da Costa Escobar |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/5099227329574183 |
dc.contributor.referee2.fl_str_mv |
Cruz, Ivana Beatrice Mânica da |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/3426369324110716 |
dc.contributor.referee3.fl_str_mv |
Biaggio, Eliara Pinto Vieira |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/6091731551273820 |
dc.contributor.referee4.fl_str_mv |
Santos Filha, Valdete Alves Valentins dos |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/3042191385044226 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0016903220423615 |
dc.contributor.author.fl_str_mv |
Gonçalves, Maiara Santos |
contributor_str_mv |
Silveira, Aron Ferreira da Hyppolito, Miguel Angelo Piccoli, Jacqueline da Costa Escobar Cruz, Ivana Beatrice Mânica da Biaggio, Eliara Pinto Vieira Santos Filha, Valdete Alves Valentins dos |
dc.subject.por.fl_str_mv |
Cisplatina Radicais livres Estresse oxidativo Apoptose Otoproteção Cóclea |
topic |
Cisplatina Radicais livres Estresse oxidativo Apoptose Otoproteção Cóclea Cisplatin Free radicals Oxidative stress Apoptosis Otoprotection Cochlea CNPQ::CIENCIAS DA SAUDE::FONOAUDIOLOGIA |
dc.subject.eng.fl_str_mv |
Cisplatin Free radicals Oxidative stress Apoptosis Otoprotection Cochlea |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FONOAUDIOLOGIA |
description |
This paper aimed to investigate the apoptosis modulation pathway and the otoprotection mechanism of N-acetylcysteine (NAC) through the analysis of the glutathione peroxidase (GSH-Px) enzyme and the Bcl-2 protein expression in outer hair cells (OHCs) of rats treated with cisplatin. The listening function was also assessed in mice under the effect of different doses of cisplatin and NAC. Two experiments were performed, named A and B, the first being over an experimental period of five days, and the second during three days. Each experiment comprised four groups, under the following protocols: group A1 (negative control): intraperitoneally saline solution 0,9%, in the same volume corresponding to cisplatin dose; group A2 (positive control): 100mg/kg/day of NAC, oral administration by gavage; group A3 (ototoxic): 3mg/kg/day of intraperitoneally cisplatin; group A4 (ototoxic with otoprotection): 100 mg/kg/day of NAC oral administration by gavage, one hour before the administration of 3 mg/kg/day of intraperitoneally cisplatin; group B1 (negative control): intraperitoneally saline solution 0,9% in the same volume corresponding to the cisplatin dose (8mg/kg/day); group B2 (positive control): 300 mg/kg/day of NAC, oral administration by gavage; group B3 (ototoxic): 8 mg/kg/day of intraperitoneally cisplatin; group B4 (ototoxic with otoprotection): 300 mg/kg/day of NAC orally by gavage, one hour before the administration of 8 mg/Kg/day of intraperitoneally cisplatin. The animals in experiment A underwent otoscopy, distortion-product otoacustic emissions (DPOAEs) and brainstem auditory evoked potential (BAEP), before and after the administration of drugs. The animals in experiment B underwent the same testing in pre- and post-treatment, their tympanic bulla being removed ant their cochleae prepared for anatomical assessment with scanning electron microscopy and immunofluorescence for labeling the GSH-Px enzyme and the Bcl-2 protein. In experiment A, it was verified that there was no significant decrease in the signal-to-noise ratio of DPOEAs, but there was a significant increase in the electrophysiologic threshold obtained through BAEP in groups A3 e A4. In experiment B, it was verified that: there was no significant increase in the electrophysiologic threshold obtained through BAEP; the OHCs remained anatomically intact; the GSH-Px enzyme showed immunostaining absent in group B1 and immunostaining present in groups B2, B3 and B4; the Bcl-2 protein showed immunostaining absent in all groups. From the results, it was concluded that the listening function was more impaired by the exposure to a subdose of cisplatin over a longer period, the apoptosis modulation pathway in outer hair cells of mice treated with cisplatin is related to the expression of the GSH-Px enzyme and not expression of the Bcl-2 protein. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-03-10 |
dc.date.accessioned.fl_str_mv |
2016-03-01 |
dc.date.available.fl_str_mv |
2016-03-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
GONÇALVES, Maiara Santos. Otoprotection by N-acetylcysteine and the apoptosis modulation pathway in hair cells of rats treated with cisplatin. 2015. 124 f. Tese (Doutorado em Fonoaudiologia) - Universidade Federal de Santa Maria, Santa Maria, 2015. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/3444 |
identifier_str_mv |
GONÇALVES, Maiara Santos. Otoprotection by N-acetylcysteine and the apoptosis modulation pathway in hair cells of rats treated with cisplatin. 2015. 124 f. Tese (Doutorado em Fonoaudiologia) - Universidade Federal de Santa Maria, Santa Maria, 2015. |
url |
http://repositorio.ufsm.br/handle/1/3444 |
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por |
language |
por |
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openAccess |
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Universidade Federal de Santa Maria |
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Programa de Pós-Graduação em Distúrbios da Comunicação Humana |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Fonoaudiologia |
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Universidade Federal de Santa Maria |
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