Conjugated linoleic acid prevents damage caused by intestinal mucositis induced by 5-fluorouracil in an experimental model

Biomed Pharmacother. 2018 Jul:103:1567-1576. doi: 10.1016/j.biopha.2018.04.133. Epub 2018 May 7.

Abstract

Background: Studies have showed the protective effects of conjugated linoleic acid (CLA) on intestinal epithelium, modulating host immune and inflammatory responses on intestinal diseases.

Objective: To evaluate the preventive effects of CLA on the intestinal mucositis induced by 5-FU in a murine model.

Methods: Sixty-four BALB/c mice were randomly divided into four groups: Control (CTL), fed a standard chow diet; CLAs, fed a diet supplemented with CLA; Mucositis (5-FU), fed a standard chow diet and underwent mucositis induction and CLAs 5-FU, fed a diet supplemented with CLA and underwent mucositis induction. Mucositis was induced by intraperitoneal injection of 300 mg/kg 5-FU. After 72 h, the animals were euthanized and intestinal permeability, bacterial translocation, inflammatory mediators, and intestinal histology were evaluated.

Results: Mice in the CLAs 5-FU group showed reduced weight loss compared to those in the 5-FU group (p < 0.005). Furthermore, the results also showed that the treatment with CLA reduced intestinal permeability, bacterial translocation, and biomarkers of inflammatory response besides minor damage to ZO-1 and occludin with maintenance of the integrity of the intestinal epithelium and a favorable balance between the inflammatory and regulatory cytokines.

Conclusion: This study suggests that CLA reduced the adverse effects from 5-FU administration on the intestinal mucosa.

Keywords: Bacterial translocation; Conjugated linoleic acids; Cytokines; Intestinal damage; Mucositis; Tight junction protein.

MeSH terms

  • Animals
  • Bacterial Translocation / drug effects
  • Body Weight / drug effects
  • Chemokines / metabolism
  • Disease Models, Animal
  • Feeding Behavior
  • Fluorouracil / adverse effects*
  • Immunoglobulin A / metabolism
  • Inflammation / pathology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Intestines / pathology*
  • Linoleic Acids, Conjugated / pharmacology
  • Linoleic Acids, Conjugated / therapeutic use*
  • Male
  • Mice, Inbred BALB C
  • Mucositis / drug therapy*
  • Mucositis / microbiology
  • Mucositis / pathology
  • Mucositis / prevention & control*
  • Tissue Distribution / drug effects

Substances

  • Chemokines
  • Immunoglobulin A
  • Linoleic Acids, Conjugated
  • Fluorouracil