The vanillin derivative VND3207 protects intestine against radiation injury by modulating p53/NOXA signaling pathway and restoring the balance of gut microbiota

Ming Li, Meng Meng Gu, Yue Lang, Jianming Shi, Benjamin P.C. Chen, Hua Guan, Lan Yu, Ping Kun Zhou, Zeng Fu Shang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The intestine is a highly radiosensitive tissue that is susceptible to structural and functional damage due to systemic as well as localized radiation exposure. Unfortunately, no effective prophylactic or therapeutic agents are available at present to manage radiation-induced intestinal injuries. We observed that the vanillin derivative VND3207 improved the survival of lethally irradiated mice by promoting intestinal regeneration and increasing the number of surviving crypts. Pre-treatment with VND3207 significantly increased the number of Lgr5+ intestinal stem cells (ISCs) and their daughter cells, the transient Ki67+ proliferating cells. Mechanistically, VND3207 decreased oxidative DNA damage and lipid peroxidation and maintained endogenous antioxidant status by increasing the level of superoxide dismutase and total antioxidant capacity. In addition, VND3207 maintained appropriate levels of activated p53 that triggered cell cycle arrest but were not sufficient to induce NOXA-mediated apoptosis, thus ensuring DNA damage repair in the irradiated small intestinal crypt cells. Furthermore, VND3207 treatment restores the intestinal bacterial flora structures altered by TBI exposure. In conclusion, VND3207 promoted intestinal repair following radiation injury by reducing reactive oxygen species-induced DNA damage and modulating appropriate levels of activated p53 in intestinal epithelial cells.

Original languageEnglish (US)
Pages (from-to)223-236
Number of pages14
JournalFree Radical Biology and Medicine
Volume145
DOIs
StatePublished - Dec 2019
Externally publishedYes

Fingerprint

Radiation Injuries
Intestines
Derivatives
Radiation
DNA Damage
DNA
Repair
Antioxidants
Bacterial Structures
Cell Cycle Checkpoints
Stem cells
DNA Repair
Lipid Peroxidation
Superoxide Dismutase
4-hydroxy-3,5-dimethoxybenzaldehyde
Gastrointestinal Microbiome
vanillin
Regeneration
Reactive Oxygen Species
Stem Cells

Keywords

  • Intestinal flora
  • NOXA
  • p53
  • Radiation-induced intestinal injuries
  • Reactive oxygen species (ROS)
  • VND3207

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

The vanillin derivative VND3207 protects intestine against radiation injury by modulating p53/NOXA signaling pathway and restoring the balance of gut microbiota. / Li, Ming; Gu, Meng Meng; Lang, Yue; Shi, Jianming; Chen, Benjamin P.C.; Guan, Hua; Yu, Lan; Zhou, Ping Kun; Shang, Zeng Fu.

In: Free Radical Biology and Medicine, Vol. 145, 12.2019, p. 223-236.

Research output: Contribution to journalArticle

Li, Ming ; Gu, Meng Meng ; Lang, Yue ; Shi, Jianming ; Chen, Benjamin P.C. ; Guan, Hua ; Yu, Lan ; Zhou, Ping Kun ; Shang, Zeng Fu. / The vanillin derivative VND3207 protects intestine against radiation injury by modulating p53/NOXA signaling pathway and restoring the balance of gut microbiota. In: Free Radical Biology and Medicine. 2019 ; Vol. 145. pp. 223-236.
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