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Related Experiment Video

Updated: Sep 10, 2025

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Ricin Toxicity to Intestinal Cells Leads to Multiple Cell Death Pathways Mediated by Oxidative Stress.

Francesco Biscotti1, Massimo Bortolotti1, Federica Falà1

  • 1Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.

Toxins
|August 27, 2025
PubMed
Summary

Ricin toxin damages intestinal cells and barrier function after ingestion. Cell death pathways involving apoptosis, necroptosis, and oxidative stress are implicated, but can be inhibited.

Keywords:
apoptosisintestinal cellsnecroptosisoxidative stressribosome-inactivating proteinsricintoxic lectins

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Area of Science:

  • Toxicology
  • Cell Biology
  • Gastroenterology

Background:

  • Ricin, a potent toxin from castor beans, poses a significant threat upon oral ingestion.
  • While systemic ricin toxicity is known, its localized gastrointestinal effects require further investigation.
  • Understanding ricin's impact on intestinal epithelial cells is crucial for assessing health risks.

Purpose of the Study:

  • To investigate the cytotoxic effects of ricin on human intestinal epithelial cell lines (HT29 and Caco-2).
  • To evaluate ricin's impact on the integrity of the intestinal epithelial barrier.
  • To elucidate the mechanisms of ricin-induced cell death, including apoptosis, necroptosis, and oxidative stress.

Main Methods:

  • Dose- and time-response assays were used to assess ricin cytotoxicity on HT29 and Caco-2 cells.
  • Trans-Epithelial Electrical Resistance (TEER) measurements evaluated epithelial barrier integrity in Caco-2 monolayers.
  • Flow cytometry analyzed cell death, and the effects of cell death inhibitors and antioxidants were tested.

Main Results:

  • Ricin exhibited high cytotoxicity against HT29 and Caco-2 cells, with nanomolar EC50 values after 24-72 hours.
  • Ricin significantly reduced TEER values in Caco-2 cells at 0.1-1 nM concentrations within 24 hours.
  • Cell death at 1 nM ricin was preventable by inhibitors (Z-VAD, necrostatin-1) and antioxidants (catalase, BHA, sodium pyruvate).

Conclusions:

  • Ricin demonstrates significant cytotoxicity and barrier-disrupting effects on human intestinal epithelial cells.
  • Apoptosis/necroptosis and oxidative stress are key mechanisms driving ricin-induced cell death in the gastrointestinal tract.
  • Inhibitors of cell death pathways and antioxidants show potential in mitigating ricin's localized toxic effects.