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Sodium formate induces development-dependent intestinal epithelial injury via necroptosis and apoptosis

Jingjing Wei1, Yuan Tian1, Meiqi Guan1

  • 1Department of Pediatrics, Shanxi Medical University, Taiyuan, People's Republic of China.

Redox Report : Communications in Free Radical Research
|December 2, 2024
PubMed

Insights

Formate in the gut may cause intestinal injury in premature infants. This study shows sodium formate damages intestinal tissue, leading to cell death, potentially contributing to necrotizing enterocolitis (NEC) in newborns.

Area of Science:

  • Gastroenterology
  • Neonatology
  • Toxicology

Background:

  • Necrotizing enterocolitis (NEC) is a critical condition in premature infants.
  • Elevated formate levels in stool are associated with NEC.
  • The role of formate in intestinal injury requires further investigation.

Purpose of the Study:

  • To investigate the role of sodium formate (NaF) in causing intestinal epithelial injury.
  • To explore the mechanisms underlying NaF-induced intestinal damage in a mouse model.

Main Methods:

  • Intraluminal injection of 150 mM NaF solution into 14-day-old and 28-day-old mice.
  • Assessment of intestinal tissue pathology, barrier function, oxidative stress markers (SOD, HO-1, MDA, 4-HNE), inflammatory cytokines (IL-1β, TNF-α, IL-6), mitochondrial function (ATP, PGC-1α), and cell death indicators (RIPK1, p-MLKL, cleaved-caspase-3, p-AKT).

Main Results:

  • NaF treatment significantly damaged intestinal epithelial tissue and barrier function.
  • Mitochondrial dysfunction, increased oxidative stress, and inflammation were observed.
  • NaF induced both necroptosis and apoptosis in a development-dependent manner.

Conclusions:

  • Formate may contribute to metabolic intestinal injury.
  • These findings suggest formate as a potential factor in the pathogenesis of NEC in human newborns.
Abstract

Keywords:
Formateapoptosisinflammation‌necroptosisnecrotizing enterocolitisoxidative stresspretermsodium formate

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