Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/jspui/handle/123456789/27208 https://doi.org/10.1371/journal.pone.0186511 |
Resumo: | Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR). DEX (0.5 or 1 mg/kg) reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and macrophage migration inhibitory factor (MIF). DEX (1 mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, transforming growth factor (TGF)-β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M), glucocorticoid-induced leucine zipper (GILZ), and mitogen-activated protein kinase (MKP1) gene expression and reduced NFκB p65 and serine threonine kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters. |
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Araújo, Aurigena Antunes deRibeiro, Susana BarbosaAraújo Júnior, Raimundo Fernandes deBrito, Gerly Anne de CastroLeitão, Renata CarvalhoBarbosa, Maisie MitcheleGarcia, Vinicius BarretoMedeiros, Aldo CunhaMedeiros, Caroline Addison Carvalho Xavier de2019-06-17T16:42:39Z2019-06-17T16:42:39Z2017-10-23ARAÚJO, Aurigena Antunes de et al.Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters. PLoS One, v. 12, p. e0186511-xx, 2017. Disponível em: <http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186511>. Acesso em: 20 mar. 2018.1932-6203https://repositorio.ufrn.br/jspui/handle/123456789/27208https://doi.org/10.1371/journal.pone.0186511engAugusta University, UNITED STATESdexamethasoneProtective effect of dexamethasone on 5-FU-induced oral mucositis in hamstersinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleOral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR). DEX (0.5 or 1 mg/kg) reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and macrophage migration inhibitory factor (MIF). DEX (1 mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, transforming growth factor (TGF)-β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M), glucocorticoid-induced leucine zipper (GILZ), and mitogen-activated protein kinase (MKP1) gene expression and reduced NFκB p65 and serine threonine kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNTEXTProtective effect of dexamethasone_2017.pdf.txtProtective effect of dexamethasone_2017.pdf.txtExtracted texttext/plain44345https://repositorio.ufrn.br/bitstream/123456789/27208/3/Protective%20effect%20of%20dexamethasone_2017.pdf.txtacf2cccb1ac40afdf01b5a0b8a931377MD53THUMBNAILProtective effect of dexamethasone_2017.pdf.jpgProtective effect of dexamethasone_2017.pdf.jpgGenerated Thumbnailimage/jpeg1754https://repositorio.ufrn.br/bitstream/123456789/27208/4/Protective%20effect%20of%20dexamethasone_2017.pdf.jpg46bf93ccb58a35b50e4d92467e2c1100MD54ORIGINALProtectiveEffectDexamethasone_Araujo_2017.pdfProtectiveEffectDexamethasone_Araujo_2017.pdfapplication/pdf22739692https://repositorio.ufrn.br/bitstream/123456789/27208/1/ProtectiveEffectDexamethasone_Araujo_2017.pdfde47dd84275b30c2232b0f3a8d72eca4MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.ufrn.br/bitstream/123456789/27208/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52123456789/272082021-11-11 16:05:01.742oai:https://repositorio.ufrn.br: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Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2021-11-11T19:05:01Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.fl_str_mv |
Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters |
title |
Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters |
spellingShingle |
Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters Araújo, Aurigena Antunes de dexamethasone |
title_short |
Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters |
title_full |
Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters |
title_fullStr |
Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters |
title_full_unstemmed |
Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters |
title_sort |
Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters |
author |
Araújo, Aurigena Antunes de |
author_facet |
Araújo, Aurigena Antunes de Ribeiro, Susana Barbosa Araújo Júnior, Raimundo Fernandes de Brito, Gerly Anne de Castro Leitão, Renata Carvalho Barbosa, Maisie Mitchele Garcia, Vinicius Barreto Medeiros, Aldo Cunha Medeiros, Caroline Addison Carvalho Xavier de |
author_role |
author |
author2 |
Ribeiro, Susana Barbosa Araújo Júnior, Raimundo Fernandes de Brito, Gerly Anne de Castro Leitão, Renata Carvalho Barbosa, Maisie Mitchele Garcia, Vinicius Barreto Medeiros, Aldo Cunha Medeiros, Caroline Addison Carvalho Xavier de |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Araújo, Aurigena Antunes de Ribeiro, Susana Barbosa Araújo Júnior, Raimundo Fernandes de Brito, Gerly Anne de Castro Leitão, Renata Carvalho Barbosa, Maisie Mitchele Garcia, Vinicius Barreto Medeiros, Aldo Cunha Medeiros, Caroline Addison Carvalho Xavier de |
dc.subject.por.fl_str_mv |
dexamethasone |
topic |
dexamethasone |
description |
Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR). DEX (0.5 or 1 mg/kg) reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and macrophage migration inhibitory factor (MIF). DEX (1 mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, transforming growth factor (TGF)-β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M), glucocorticoid-induced leucine zipper (GILZ), and mitogen-activated protein kinase (MKP1) gene expression and reduced NFκB p65 and serine threonine kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017-10-23 |
dc.date.accessioned.fl_str_mv |
2019-06-17T16:42:39Z |
dc.date.available.fl_str_mv |
2019-06-17T16:42:39Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ARAÚJO, Aurigena Antunes de et al.Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters. PLoS One, v. 12, p. e0186511-xx, 2017. Disponível em: <http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186511>. Acesso em: 20 mar. 2018. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/jspui/handle/123456789/27208 |
dc.identifier.issn.none.fl_str_mv |
1932-6203 |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1371/journal.pone.0186511 |
identifier_str_mv |
ARAÚJO, Aurigena Antunes de et al.Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters. PLoS One, v. 12, p. e0186511-xx, 2017. Disponível em: <http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186511>. Acesso em: 20 mar. 2018. 1932-6203 |
url |
https://repositorio.ufrn.br/jspui/handle/123456789/27208 https://doi.org/10.1371/journal.pone.0186511 |
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eng |
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eng |
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openAccess |
dc.publisher.none.fl_str_mv |
Augusta University, UNITED STATES |
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Augusta University, UNITED STATES |
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