Protective Effect of Cashew Gum (Anacardium occidentale L.) on 5-Fluorouracil-Induced Intestinal Mucositis

João Antônio Leal de Miranda; João Erivan Façanha Barreto; Dainesy Santos Martins; Paulo Vitor de Souza Pimentel; Deiziane Viana da Silva Costa; Reyca Rodrigues E Silva; Luan Kelves Miranda de Souza; Camila Nayane Carvalho de Lima; Jefferson Almeida Rocha; Ana Paula Fragoso de Freitas; Durcilene Alves da Silva; Ariel Gustavo Scafuri; Renata Ferreira Carvalho de Leitão; Gerly Anne de Castro Brito; Jand Venes Rolim Medeiros; Gilberto Santos Cerqueira

doi:10.3390/ph12020051

Protective Effect of Cashew Gum (Anacardium occidentale L.) on 5-Fluorouracil-Induced Intestinal Mucositis

Pharmaceuticals (Basel). 2019 Apr 3;12(2):51. doi: 10.3390/ph12020051.

Authors

João Antônio Leal de Miranda^{1

2}, João Erivan Façanha Barreto¹, Dainesy Santos Martins³, Paulo Vitor de Souza Pimentel⁴, Deiziane Viana da Silva Costa⁵, Reyca Rodrigues E Silva⁶, Luan Kelves Miranda de Souza⁷, Camila Nayane Carvalho de Lima⁸, Jefferson Almeida Rocha⁹, Ana Paula Fragoso de Freitas¹⁰, Durcilene Alves da Silva⁶, Ariel Gustavo Scafuri¹¹, Renata Ferreira Carvalho de Leitão¹², Gerly Anne de Castro Brito¹³, Jand Venes Rolim Medeiros¹⁴, Gilberto Santos Cerqueira^{15

16}

Affiliations

¹ Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro de Farias Street, Porangabuçu Campus, 60416-030 Fortaleza, Brazil. joaoantonio@ufpi.edu.br.
² Biotechnology and Biodiversity Center Research, BIOTEC, Federal University of Piauí, Parnaíba, 64202-020 Piauí, Brazil. joaoantonio@ufpi.edu.br.
³ Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro de Farias Street, Porangabuçu Campus, 60416-030 Fortaleza, Brazil. dainy.santos@gmail.com.
⁴ Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro de Farias Street, Porangabuçu Campus, 60416-030 Fortaleza, Brazil. paulo_vitordesouza@hotmail.com.
⁵ Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro de Farias Street, Porangabuçu Campus, 60416-030 Fortaleza, Brazil. deiziane2009@gmail.com.
⁶ Biotechnology and Biodiversity Center Research, BIOTEC, Federal University of Piauí, Parnaíba, 64202-020 Piauí, Brazil. reyca_14@hotmail.com.
⁷ Biotechnology and Biodiversity Center Research, BIOTEC, Federal University of Piauí, Parnaíba, 64202-020 Piauí, Brazil. luankelves11@gmail.com.
⁸ Nucleus of Research and Development of Medications (NPDM), Federal University of Ceará, Coronel Nunes de Melo Street, 100, 60430-275 Fortaleza, Brazil. camilacarvalhoenf@yahoo.com.br.
⁹ Research Group in Natural Sciences and Biotechnology, Federal University of Maranhão, s/n Avenue Aurila Maria Santos Barros de Sousa, Frei Alberto Beretta, 65940-000 Grajaú-MA, Brazil. jeffersonkalel@hotmail.com.
¹⁰ Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro de Farias Street, Porangabuçu Campus, 60416-030 Fortaleza, Brazil. paulinhaff2@hotmail.com.
¹¹ Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro de Farias Street, Porangabuçu Campus, 60416-030 Fortaleza, Brazil. urologia@gmail.com.
¹² Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro de Farias Street, Porangabuçu Campus, 60416-030 Fortaleza, Brazil. leitao_renata@yahoo.com.br.
¹³ Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro de Farias Street, Porangabuçu Campus, 60416-030 Fortaleza, Brazil. gerlybrito@hotmail.com.
¹⁴ Biotechnology and Biodiversity Center Research, BIOTEC, Federal University of Piauí, Parnaíba, 64202-020 Piauí, Brazil. camilacarvalhoenf@yahoo.com.br.
¹⁵ Department of Morphology, Faculty of Medicine, Federal University of Ceará, s/n Delmiro de Farias Street, Porangabuçu Campus, 60416-030 Fortaleza, Brazil. giufarmacia@hotmail.com.
¹⁶ Biotechnology and Biodiversity Center Research, BIOTEC, Federal University of Piauí, Parnaíba, 64202-020 Piauí, Brazil. giufarmacia@hotmail.com.

Abstract

Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU), a chemotherapeutic agent used for cancer treatment. Cashew gum (CG) has been reported as a potent anti-inflammatory agent. In the present study, we aimed to evaluate the effect of CG extracted from the exudate of Anacardium occidentale L. on experimental intestinal mucositis induced by 5-FU. Swiss mice were randomly divided into seven groups: Saline, 5-FU, CG 30, CG 60, CG 90, Celecoxib (CLX), and CLX + CG 90 groups. 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), and glutathione (GSH), and immunohistochemical analysis of interleukin 1 beta (IL-1β) and cyclooxygenase-2 (COX-2). 5-FU induced intense weight loss and reduction in villus height compared to the saline group. CG 90 prevented 5-FU-induced histopathological changes and decreased oxidative stress through decrease of MDA levels and increase of GSH concentration. CG attenuated inflammatory process by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. Our findings suggest that CG at a concentration of 90 mg/kg reverses the effects of 5-FU-induced intestinal mucositis.

Keywords: 5-fluorouracil; heteropolysaccharide; inflammation; intestinal mucositis.