The synergystic effects of omega-3 fatty acids against 5-fluorouracil-induced mucosal impairment in mice

Background: Anti-cancer pharmaceuticals frequently have adverse side effects on patients such as gastrointestinal involvement limiting their clinical applications. These effects may be controlled by nutritional interventions, however, there are few studies that have shown any mechanistic effects. In this study, we examined effects of diet enhanced with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on 5-fluorouracil (5-FU)-induced intestinal impairment and immunity in mice. Methods: C57Bl6 mice were randomized to control diet, control diet + EPA, control + DHA, control + fish oil, or diet enchanced with DHA/EPA. After seven days of each respective diet, mice, excluding those in the sham group, were treated with 10 mg/kg/day 5-FU for 7 days. The effects of 5-FU-induced impairment in the small intestine were assessed using cytokine concentrations in serum and tissue, secretory immunoglobulin (Ig) A, diamine oxidase (DAO) activity, the length of the small intestine, and the expression of apoptosis signaling genes. Results: The EPA/DHA-enhanced diet resulted in the most beneficial, synergystic and protective effect against 5-FU induced weight loss. Protection against inflammation, impaired intestinal function, and immunity of the small intestine were also observed. Individually, a DHA-enriched diet demonstrated a protective effect against 5-FU damage with longer small intestine mucosal and crypt lengths, greater DAO activity, and higher IgA concentrations, whereas the EPA-enriched diet resulted in decreased inflammatory cytokine concentrations in both plasma and small intestine and expression of apoptosis target genes. Conclusions: In conclusion, a diet enhanced with EPA and DHA results in synergism protecting against the detrimental effects of 5-FU and limiting chemotherapy induced mucosal impairment. Keyword: Omega-3 fatty acids, 5-fluorouracil, Mucosal impairment, Small intestine