Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress
Lázaro de Sousa Fideles,
João Antônio Leal de Miranda,
Conceição da Silva Martins,
Maria Lucianny Lima Barbosa,
Helder Bindá Pimenta,
Paulo Vitor de Souza Pimentel,
Claudio Silva Teixeira,
Marina Alves Sampaio Scafuri,
Samuel de Osterno Façanha,
João Erivan Façanha Barreto,
Poliana Moreira de Medeiros Carvalho,
Ariel Gustavo Scafuri,
Joabe Lima Araújo,
Jefferson Almeida Rocha,
Icaro Gusmão Pinto Vieira,
Nágila Maria Pontes Silva Ricardo,
Matheus da Silva Campelo,
Maria Elenir Nobre Pinho Ribeiro,
Gerly Anne de Castro Brito,
Gilberto Santos Cerqueira
Affiliations
Lázaro de Sousa Fideles
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
João Antônio Leal de Miranda
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
Conceição da Silva Martins
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
Maria Lucianny Lima Barbosa
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
Helder Bindá Pimenta
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
Paulo Vitor de Souza Pimentel
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
Claudio Silva Teixeira
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
Marina Alves Sampaio Scafuri
Scafuri Institute of Human Sexuality, 1513 Republic of Lebanon Street, Varjota, Fortaleza 60175-222, Brazil
Samuel de Osterno Façanha
Christus University Center (Unichristus), 133 Adolfo Gurgel Street, Fortaleza 63010-475, Brazil
João Erivan Façanha Barreto
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
Poliana Moreira de Medeiros Carvalho
University Center of Juazeiro do Norte (UNIJUAZEIRO), 1224 San Francisco Street, Juazeiro do Norte-CE 63010-475, Brazil
Ariel Gustavo Scafuri
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
Joabe Lima Araújo
Department of Genetics and Morphology, s/n Darcy Ribeiro University Campus, University of Brasília, Brasília-DF 70910-900, Brazil
Jefferson Almeida Rocha
Medicinal Chemistry and Biotechnology Research Group (QUIMEBIO), Federal University of Maranhão (UFMA), São Bernardo/MA 65550-000, Brazil
Icaro Gusmão Pinto Vieira
Technological Development Park, Federal University of Ceará, Humberto Monte Avenue, 2977, Pici Campus, Fortaleza 60440-900, Brazil
Nágila Maria Pontes Silva Ricardo
Department of Organic and Inorganic Chemistry, Federal University of Ceará, Pici Campus, Fortaleza 60440-900, Brazil
Matheus da Silva Campelo
Department of Organic and Inorganic Chemistry, Federal University of Ceará, Pici Campus, Fortaleza 60440-900, Brazil
Maria Elenir Nobre Pinho Ribeiro
Department of Organic and Inorganic Chemistry, Federal University of Ceará, Pici Campus, Fortaleza 60440-900, Brazil
Gerly Anne de Castro Brito
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
Gilberto Santos Cerqueira
Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro of Farias Street, Porangabuçu Campus, Fortaleza 60416-030, Brazil
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.
