Dietary supplementation with omega-3 fatty acid attenuates 5-fluorouracil induced mucositis in mice

Abstract

BackgroundStudies showed the positive effects of omega-3 fatty acid (n-3 FA) for the treatment of inflammatory bowel disease as it alleviated the symptoms and promoted better mucosal integrity. The objective of this study was to determine whether a diet with the addition of n-3 FA helps control the inflammation observed in 5-fluorouracil (5-FU) induced mucositis.MethodsBALB/c mice were randomly divided into four groups as follows: 1: control (CTL), fed a standard chow diet; 2: CTL + n-3 FA – n-3 FA, fed a diet with n-3; 3: mucositis (MUC), fed a standard chow diet and subjected to mucositis; and 4: MUC+ n-3 FA, fed a diet with n-3 FA and subjected to mucositis. On the 8th day, the animals of the MUC and MUC + n-3 FA groups received an intraperitoneal injection of 300 mg/kg 5-FU for mucositis induction. After 24 h or 72 h, all mice were euthanized and evaluated for intestinal permeability, bacterial translocation, intestinal histology and apoptosis.ResultsMice that received the diet with n-3 FA and a 5-FU injection showed less weight loss compared to the animals of the MUC group (p < 0.005). Decreased intestinal permeability and bacterial translocation were also observed in animals fed n-3 FA, and these mice underwent mucositis compared to the MUC group (p < 0.005). These data were associated with mucosal integrity and a reduced number of apoptotic cells in the ileum mucosa compared to the mice that received the control diet and 5-FU injection.ConclusionTogether, these results show that omega-3 fatty acid decreases the mucosal damage caused by 5-FU-induced 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.…”

Quercetin prevents small intestinal damage and enhances intestinal recovery during methotrexate-induced intestinal mucositis of rats

“…The pathogenesis of chemotherapy-induced gastrointestinal mucositis has been described by Sonis et al ( 36 ) and includes five phases: initiation by chemotherapy, upregulation and generation of messenger signals, signaling by pro-inflammatory cytokines and amplification of mucosal injury, ulceration of the mucosa, and finally healing. Several experiments evaluated the relationship between intestinal permeability, bacterial translocation, intestinal histology, and apoptosis during intestinal mucositis ( 37 ). Further experiments are required to determine whether positive effect of QCT in preventing intestinal damage is related to decreasing intestinal permeability as well as to decreased generation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8), decreased activation of NFκB signaling, decreased leukocyte chemotaxis, and decreased T-cell reactivity, which were described in an animal model of inflammatory bowel disease.…”

Intestinal permeability to iohexol as an in vivo marker of chemotherapy-induced gastrointestinal toxicity in Sprague–Dawley rats

“…This can also be the case regarding 5-FU and oxaliplatin although little is known about their effects on tight junctional proteins. 5-FU increases intestinal permeability to technetium-labeled diethylene-triamine-pentaacetate (Tc-99 m-DTPA) in mice [ 30 , 31 ] and to chromium-labeled ethylenediaminetetraacetate ( 51 Cr-EDTA) in humans [ 6 , 25 ] but the role of tight junctional protein expression in this process remains uncharacterized. The data regarding the effects of oxaliplatin are even scarcer and to our knowledge this is the first study to show that oxaliplatin causes a significant increase in intestinal permeability.…”