Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

João  Antônio Leal de Miranda; Conceição  da Silva Martins; Lázaro  de Sousa Fideles; Maria  Lucianny Lima Barbosa; João  Erivan Façanha Barreto; Helder  Bindá Pimenta; Francisco  Orlando Rafael Freitas; Paulo  Vitor de Souza Pimentel; Claudio  Silva Teixeira; Ariel  Gustavo Scafuri; Maria  Claudia dos Santos Luciano; 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

doi:10.3390/ph13010010

Pharmaceuticals (Jan 2020)

Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

João Antônio Leal de Miranda,
Conceição da Silva Martins,
Lázaro de Sousa Fideles,
Maria Lucianny Lima Barbosa,
João Erivan Façanha Barreto,
Helder Bindá Pimenta,
Francisco Orlando Rafael Freitas,
Paulo Vitor de Souza Pimentel,
Claudio Silva Teixeira,
Ariel Gustavo Scafuri,
Maria Claudia dos Santos Luciano,
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

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
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
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
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
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
Francisco Orlando Rafael Freitas: 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
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
Maria Claudia dos Santos Luciano: Nucleus of Research and Development of Medications (NPDM), Federal University of Ceará, Coronel Nunes of Melo Street, 100, Fortaleza 60430-275, Brazil
Joabe Lima Araújo: Research Group in Natural Sciences and Biotechnology, Federal University of Maranhão, s/n Avenue Aurila Maria Santos Barros of Sousa, Frei Alberto Beretta, Grajaú-MA 65940-000, Brazil
Jefferson Almeida Rocha: Research Group in Natural Sciences and Biotechnology, Federal University of Maranhão, s/n Avenue Aurila Maria Santos Barros of Sousa, Frei Alberto Beretta, Grajaú-MA 65940-000, 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

DOI: https://doi.org/10.3390/ph13010010
Journal volume & issue: Vol. 13, no. 1
p. 10

Abstract

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Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU), a chemotherapeutic agent used for cancer treatment. Troxerutin (TRX), a semi-synthetic flavonoid extracted from Dimorphandra gardneriana, has been reported as a potent antioxidant and anti-inflammatory agent. In the present study, we aimed to evaluate the effect of TRX on 5-FU-induced intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, TRX-50, TRX-100, TRX-150, Celecoxib (CLX), and CLX + TRX-100. The weight of mice was measured daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis), levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), mast and goblet cell counts, immunohistochemical analysis, and cyclooxygenase-2 (COX-2) activity. Compared to the saline treatment, the 5-FU treatment induced intense weight loss and reduction in villus height. TRX treatment (100 mg/kg) prevented the 5-FU-induced histopathological changes and decreased oxidative stress by decreasing the MDA levels and increasing GSH concentration. TRX attenuated inflammatory process by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. TRX also reversed the depletion of goblet cells. Our findings suggest that TRX at a concentration of 100 mg/kg had chemopreventive effects on 5-FU-induced intestinal mucositis via COX-2 pathway.

Published in Pharmaceuticals

ISSN: 1424-8247 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica
Website: http://www.mdpi.com/journal/pharmaceuticals/

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