Título:	Role of rutin in 5-Fluorouracil-induced intestinal mucositis : prevention of histological damage and reduction of inflammation and oxidative stress
Autor(es):	Fideles, Lázaro de Sousa Miranda, João Antônio Leal de 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 Campelo, Matheus da Silva Ribeiro, Maria Elenir Nobre Pinho Brito, Gerly Anne de Castro Cerqueira, Gilberto Santos
ORCID:	https://orcid.org/0000-0002-0273-4169 https://orcid.org/0000-0003-1652-6544 https://orcid.org/0000-0003-1863-5701 https://orcid.org/0000-0002-4806-9192 https://orcid.org/0000-0003-1849-5403 https://orcid.org/0000-0003-0286-1974 https://orcid.org/0000-0001-6896-7179 https://orcid.org/0000-0002-8214-4379 https://orcid.org/0000-0001-6717-3772
Assunto:	Flavonóides Inflamação Intestinos
Data de publicação:	17-Jun-2020
Editora:	MDPI
Referência:	FIDELES, Lázaro de Sousa et al. Role of rutin in 5-Fluorouracil-induced intestinal mucositis: prevention of histological damage and reduction of inflammation and oxidative stress. Molecules, v. 25, n. 12, 2786, 2020. DOI: https://doi.org/10.3390/molecules25122786. Disponível em: https://www.mdpi.com/1420-3049/25/12/2786. Acesso em: 15 jan. 2021.
Abstract:	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.
Licença:	© 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/).
DOI:	https://doi.org/10.3390/molecules25122786
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