Monosodium glutamate induces oxidative stress, protein folding defects, mitochondrial dysfunction and cell death in intestinal epithelial cells

Creative Commons License

Zhao B., Babayev H., Zeyneloglu C., Pat Y., Yazıcı D., Ardıçlı S., ...More

Swiss Medical Weekly, vol.155, no.s289, pp.19, 2025 (SCI-Expanded, Scopus)

  • Publication Type: Article / Article
  • Volume: 155 Issue: s289
  • Publication Date: 2025
  • Journal Name: Swiss Medical Weekly
  • Journal Indexes: Scopus, Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, MEDLINE, Directory of Open Access Journals
  • Page Numbers: pp.19
  • Open Archive Collection: AVESIS Open Access Collection
  • Bursa Uludag University Affiliated: Yes

Abstract

Aim: Environmental exposures can impair epithelial barriers and contribute to disease. Here, we report the impact of monosodium glutamate (MSG), disodium guanylate (DSG), disodium inosinate (DSI), and their combined effects on intestinal epithelial cells.

Methods: Monolayer Caco-2 cells and an organ-on-a-chip model were established, and cellular cytotoxicity, transepithelial electrical resistance (TEER), paracellular flux (PF), RNA-sequencing, and reactive oxygen species (ROS) detection were performed at consumer-relevant doses.

Results: MSG, DSG, DSI, and their combination caused cytotoxicity at 1%, 0.5%, 2%, and 0.5%, respectively. A one-day exposure to 1% MSG, 1% DSG, or the 1% doses of combined compounds reduced TEER. After three days, 1% MSG and the combined treatment significantly increased PF, indicating compromised barrier integrity. RNA-sequencing transcriptome revealed significant differences in gene expression between the 1% MSG and the combined exposure groups compared to controls. Key pathways affected by 1% MSG included oxidative stress, unfolded protein response, and mitochondrial dysfunction. Increased ROS levels after 24 hours of MSG exposure were significantly reduced with 4 mM N-acetyl-L-cysteine. Autophagy regulation and upregulation of Deptor and TORC1 signaling were also observed.

Conclusions: Food flavor enhancers induce cytotoxicity, cellular stress, and barrier damage in gut epithelial cells. These findings raise concerns about their potential role in microbial imbalance, immune dysfunction, and inflammation.