Peroxisome proliferator activated receptor-gamma stimulation for prevention of 5-fluorouracil-induced oral mucositis in mice

Head Neck. 2018 Mar;40(3):577-583. doi: 10.1002/hed.25017. Epub 2017 Nov 20.

Abstract

Background: Oral mucositis is a side effect of treatment regimens containing 5-fluorouracil (5-FU). The purpose of this study was to present our evaluation to see if rosiglitazone (RGZ) protected normal tissues from chemotherapy-induced oral mucositis.

Methods: C57BL/6J mice were treated with 5-FU for 5 days, with or without RGZ. Mice were euthanized after 5, 8, 11, or 15 days, and mucosal segments were collected.

Results: The RGZ did not affect the 5-FU-induced decrease in mouse body weight. The 5-FU caused loss of epithelial architecture, collagen fiber impairment, and inflammatory infiltration. The RGZ reduced leukocyte infiltration, preserved tissue structure, and dampened the 5-FU-induced expression of p53 and matrix metalloproteinase (Mmp)-2 after 5 days, and of Mmp-2 and interleukin (Il-1β after 15 days. The RGZ inhibited the 5-FU-induced increase of transforming growth factor-beta (TGF-β) and nuclear factor-kappa B (NF-κB) proteins and restored collagen protein levels.

Conclusion: The RGZ had a protective effect on oral mucosa damaged by chemotherapy. These data encourage the further study of RGZ for the prevention of 5-FU-induced mucositis in patients with cancer.

Keywords: 5-fluorouracil (5-FU); chemotherapy toxicity; oral mucositis; peroxisome proliferator activated receptor-gamma (PPAR-γ) agonist; rosiglitazone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cytokines / metabolism
  • Fluorouracil / adverse effects*
  • Fluorouracil / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mouth Mucosa / drug effects
  • Mouth Mucosa / metabolism
  • Mouth Mucosa / pathology
  • PPAR gamma / agonists*
  • Real-Time Polymerase Chain Reaction
  • Rosiglitazone / pharmacology*
  • Stomatitis / chemically induced*
  • Stomatitis / prevention & control

Substances

  • Cytokines
  • PPAR gamma
  • Rosiglitazone
  • Fluorouracil