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

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.

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

“…Several studies have described the histopathological and morphometric alterations promoted by 5-FU, such as reduction and vacuolization of intestinal villi, crypt necrosis, inflammatory cell infiltration, edema, loss of cell architecture, and decrease in villus/crypt ratio [34][35][36][37][38][39]. Our findings are consistent with those presented in these studies.…”

Chemical Characterization and Anti-inflammatory Assessment of the Hydroethanolic Extract of Fridericia chica

“…2e). An increased rate of apoptosis in the mucositis group was observed compared with controls, as described by previous reports (Santos Miranda et al 2019). Furthermore, preservation of the tissue architecture following administration of the analyzed plant extract was comparable with studies using other species, such as Bidens pilosa (Ávila et al 2015) and Curcuma longa (Bastos et al 2016).…”

“…3a). Similar results have been found with the use of plant extracts to reduce the damage caused by chemotherapeutic drugs, e.g., grape seed extract (Cheah et al 2009), B. pilosa (Ávila et al 2015), C. longa (Bastos et al 2016), and Anacardium occidentale (Miranda et al 2019). In addition to weight loss, chemotherapy administration also induces enterocyte apoptosis and reduces the expression of proteins that control the integrity of the mucosa, promoting breaks in the intestinal epithelium and leading to increased intestinal permeability (Barros et al 2018).…”

“…4b) were significantly increased in the 5-FU-treated group (p < 0.01), demonstrating strong inflammatory activity. Animals from the plant extract treatment plus 5-FU group presented decreased MPO and EPO levels compared with control animals, both exhibiting physiological levels, and indicating a reduced inflammatory response, which has been previously observed using other treatment options (Bastos et al 2016;Santos Filho et al 2016;Miranda et al 2019). By reducing leukocyte infiltration, flavonoids can attenuate reactive oxygen species (ROS) production, cyclooxygenase-2 (COX-2) activation, and prostaglandins release, producing local benefits by maintaining tissue integrity.…”

Special Issue “Anticancer Drugs”

“…Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU) treatment, a chemotherapeutic agent used for colon, oesophageal, stomach, breast, pancreatic, and cervical cancers. Miranda et al have evaluated the effects of Cashew gum (bark exudate from Anacardium occidentale L.) as a potent anti-inflammatory agent on experimental intestinal mucositis induced by 5-FU [7]. Use of Cashew gum, as a versatile polymer scaffold material in formulating pharmaceuticals, is of considerable interest owing to the polymer’s biocompatibility, low toxicity, and biodegradability.…”