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Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress
Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from Dimorphandra gardneriana, exhibits antioxidant, anti...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356626/ https://www.ncbi.nlm.nih.gov/pubmed/32560278 http://dx.doi.org/10.3390/molecules25122786 |
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author | Fideles, Lázaro de Sousa de Miranda, João Antônio Leal Martins, Conceição da Silva Barbosa, Maria Lucianny Lima Pimenta, Helder Bindá Pimentel, Paulo Vitor de Souza Teixeira, Claudio Silva Scafuri, Marina Alves Sampaio Façanha, Samuel de Osterno Barreto, João Erivan Façanha Carvalho, Poliana Moreira de Medeiros Scafuri, Ariel Gustavo Araújo, Joabe Lima Rocha, Jefferson Almeida Vieira, Icaro Gusmão Pinto Ricardo, Nágila Maria Pontes Silva da Silva Campelo, Matheus Ribeiro, Maria Elenir Nobre Pinho de Castro Brito, Gerly Anne Cerqueira, Gilberto Santos |
author_facet | Fideles, Lázaro de Sousa de Miranda, João Antônio Leal Martins, Conceição da Silva Barbosa, Maria Lucianny Lima Pimenta, Helder Bindá Pimentel, Paulo Vitor de Souza Teixeira, Claudio Silva Scafuri, Marina Alves Sampaio Façanha, Samuel de Osterno Barreto, João Erivan Façanha Carvalho, Poliana Moreira de Medeiros Scafuri, Ariel Gustavo Araújo, Joabe Lima Rocha, Jefferson Almeida Vieira, Icaro Gusmão Pinto Ricardo, Nágila Maria Pontes Silva da Silva Campelo, Matheus Ribeiro, Maria Elenir Nobre Pinho de Castro Brito, Gerly Anne Cerqueira, Gilberto Santos |
author_sort | Fideles, Lázaro de Sousa |
collection | PubMed |
description | Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from Dimorphandra gardneriana, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis. |
format | Online Article Text |
id | pubmed-7356626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73566262020-07-22 Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress Fideles, Lázaro de Sousa de Miranda, João Antônio Leal Martins, Conceição da Silva Barbosa, Maria Lucianny Lima Pimenta, Helder Bindá Pimentel, Paulo Vitor de Souza Teixeira, Claudio Silva Scafuri, Marina Alves Sampaio Façanha, Samuel de Osterno Barreto, João Erivan Façanha Carvalho, Poliana Moreira de Medeiros Scafuri, Ariel Gustavo Araújo, Joabe Lima Rocha, Jefferson Almeida Vieira, Icaro Gusmão Pinto Ricardo, Nágila Maria Pontes Silva da Silva Campelo, Matheus Ribeiro, Maria Elenir Nobre Pinho de Castro Brito, Gerly Anne Cerqueira, Gilberto Santos Molecules Article Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from Dimorphandra gardneriana, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis. MDPI 2020-06-17 /pmc/articles/PMC7356626/ /pubmed/32560278 http://dx.doi.org/10.3390/molecules25122786 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fideles, Lázaro de Sousa de Miranda, João Antônio Leal Martins, Conceição da Silva Barbosa, Maria Lucianny Lima Pimenta, Helder Bindá Pimentel, Paulo Vitor de Souza Teixeira, Claudio Silva Scafuri, Marina Alves Sampaio Façanha, Samuel de Osterno Barreto, João Erivan Façanha Carvalho, Poliana Moreira de Medeiros Scafuri, Ariel Gustavo Araújo, Joabe Lima Rocha, Jefferson Almeida Vieira, Icaro Gusmão Pinto Ricardo, Nágila Maria Pontes Silva da Silva Campelo, Matheus Ribeiro, Maria Elenir Nobre Pinho de Castro Brito, Gerly Anne Cerqueira, Gilberto Santos Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress |
title | Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress |
title_full | Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress |
title_fullStr | Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress |
title_full_unstemmed | Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress |
title_short | Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress |
title_sort | role of rutin in 5-fluorouracil-induced intestinal mucositis: prevention of histological damage and reduction of inflammation and oxidative stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356626/ https://www.ncbi.nlm.nih.gov/pubmed/32560278 http://dx.doi.org/10.3390/molecules25122786 |
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