Resveratrol attenuates radiation enteritis through the SIRT1/FOXO3a and PI3K/AKT signaling pathways

Biochem Biophys Res Commun. 2021 May 21:554:199-205. doi: 10.1016/j.bbrc.2021.03.122. Epub 2021 Mar 31.

Abstract

Radiation enteritis (RE) is the most common radiotherapy complication, and effective RE treatments are lacking. Resveratrol exerts beneficial effects on radiation injury. However, the effect of resveratrol in radiation-induced intestinal injury and the underlying mechanism remain unclear. Here, a C57BL/6 mouse model of RE was established and an intestinal epithelial cell line was used to evaluate the protective effects of resveratrol against radiation-induced intestinal injury and the underlying mechanisms. Resveratrol improved radiation-induced oxidative stress and cell apoptosis via upregulating antioxidant enzymes and downregulating p53 acetylation. In vivo, resveratrol-treated mice exhibited longer survival; longer villi; more intestinal crypt cells; upregulated expression of Ki67, catalase, and superoxide dismutase 2; and fewer inflammatory proteins and apoptotic cells. These protective effects were suppressed by inhibition of SIRT1. These results demonstrate that resveratrol can reduce radiation-induced intestinal injury by inhibiting oxidative stress and apoptosis via the SIRT1/FOXO3a and PI3K/AKT pathways.

Keywords: Oxidative stress; PI3K/AKT pathway; Radiation enteritis; Radioprotection; Resveratrol; SIRT1/FOXO3a signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis
  • Cell Line
  • Disease Models, Animal
  • Enteritis / etiology
  • Enteritis / metabolism
  • Enteritis / pathology
  • Enteritis / prevention & control*
  • Forkhead Box Protein O3 / metabolism*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / radiation effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Radiation Injuries, Experimental / etiology
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology
  • Radiation Injuries, Experimental / prevention & control*
  • Radiation, Ionizing
  • Rats
  • Resveratrol / pharmacology*
  • Signal Transduction
  • Sirtuin 1 / metabolism*

Substances

  • Antioxidants
  • Forkhead Box Protein O3
  • FoxO3 protein, mouse
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Resveratrol