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

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

doi:10.3390/ph12020051

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.

Highlights

Cancer, a complex disease characterized by uncontrolled cell growth, is one of the main causes of morbidity and mortality in both developed and developing countries [1,2,3]
From the second day, all mice subjected to 5-FU-induced intestinal mucositis presented progressive weight loss, which was significant compared to the saline group (p < 0.05)
We investigated the effects of Cashew gum (CG) (90 mg/kg) in the presence or absence of CLX on COX-2 and IL-1β expression during 5-FU-induced intestinal mucositis through immunohistochemical analysis. 5-FU promoted intense immunostaining of COX-2 (Figure 6C) and IL-1β (Figure 6D) in the duodenal mucosa compared to the saline group (Figure 6A,B,K,L, p < 0.05)

Summary

Introduction

A complex disease characterized by uncontrolled cell growth, is one of the main causes of morbidity and mortality in both developed and developing countries [1,2,3]. 5-FU is a fluorinated pyrimidine with antimetabolite activity. 5-fluorouracil (5-FU) is one of the major chemotherapeutic agents used for the treatment of cancer. It can cause side effects such as nausea, vomiting, diarrhea, myelosuppression, and intestinal mucositis [4,5,6,7,8,9]. Mucositis is initiated by basal cell lesions in the gastrointestinal tract, resulting in mucosal damage, intense inflammatory reaction, and consequent ulceration. It affects around 40% of patients treated with chemotherapeutic agents [10,11]. Intestinal mucositis can increase the risk of bacterial translocation and sepsis, impairing the continuity of anticancer treatment

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