Can ochratoxin A and trichothecene mycotoxins cause oxidative stress, barrier disruption, and immune signaling changes?

Ochratoxin A (OTA) and trichothecene mycotoxins are food- and environment-associated fungal metabolites. Experimental evidence supports the claim that they can affect redox balance, intestinal epithelial integrity, and immune signaling, but these effects are highly dependent on toxin identity, concentration, exposure duration, and experimental model.

Experimental and mechanistic evidence

• Oxidative and mitochondrial stress: OTA increases reactive oxygen species, lipid-peroxidation markers, and mitochondrial dysfunction, including reduced membrane potential, impaired respiration, and lower ATP production. In primary human kidney proximal-tubule cells, oxidative phosphorylation was impaired at low-nanomolar OTA exposure in vitro. DON and NIV also increase ROS; in rat intestinal cells, NIV and combined NIV–DON exposure produced stronger oxidative/inflammatory responses than DON alone.
• Barrier disruption: In differentiated Caco-2 monolayers, OTA reduced transepithelial electrical resistance over 24 hours and increased 4-kDa dextran flux approximately threefold at the largest reported effect (100 μM). OTA reduced claudin-3/claudin-4, while DON impairs barrier function through MAPK-associated claudin-4 loss. OTA also altered ZO-1 and occludin in porcine intestinal cells through a ROS/Ca²⁺/MLCK-associated pathway.
• Immune signaling: OTA modulates NF-κB, ERK, and p38 signaling. In porcine macrophages, 24-hour exposure increased cytokines, migration, and phagocytosis, whereas 72-hour exposure produced an M2-like, lower-cytokine, less-phagocytic state. Trichothecenes bind ribosomes and inhibit protein synthesis, triggering ribotoxic stress with p38/JNK/ERK activation; lower exposures may induce cytokines, while higher exposures can favor apoptosis and immune suppression.

Human relevance

• These findings do not establish comparable injury or inflammation at usual human dietary exposures. Biomonitoring demonstrates exposure but not oxidative injury, barrier failure, or systemic inflammatory causality.

Bottom line

• The claim is supported in experimental systems: OTA and several trichothecenes, especially DON and NIV, can promote oxidative/mitochondrial stress, weaken intestinal tight junctions, and alter immune signaling; translating these mechanisms to real-world human health effects requires caution.