Can aflatoxin and ochratoxin A promote oxidative stress and weaken glutathione defenses?

Mycotoxins are food-contaminant exposures of toxicological concern. The claim is substantially supported for oxidative stress, particularly in experimental systems; evidence for depletion of glutathione-dependent defenses is stronger for aflatoxin than for ochratoxin A.

Clinical and experimental evidence

• Aflatoxin B1 increases reactive oxygen species (ROS) and oxidative-damage markers in experimental models. A 2025 Caco-2 intestinal-cell study found increased superoxide. Human occupational studies report higher malondialdehyde (MDA) and lower glutathione (GSH) or total antioxidant capacity in exposed workers, but their cross-sectional design cannot establish causation.
• In ex-vivo blood cultures from five donors, aflatoxin B1 increased MDA while reducing GSH and antioxidant-enzyme activity. This supports a direct biologic effect, although it does not quantify effects under typical dietary exposure conditions.
• Ochratoxin A (OTA) also increased superoxide in Caco-2 cells. Human-derived HepG2-cell and animal-tissue studies show altered glutathione and antioxidant-enzyme measures, consistent with oxidative injury, but do not demonstrate systemic effects in exposed people.

Mechanistic interpretation

• ROS detoxification requires GSH. Aflatoxin may therefore reduce GSH availability both through oxidative burden and through glutathione-S-transferase–mediated detoxification of the toxin.
• For OTA, proposed mechanisms include mitochondrial electron-transport disruption, impaired mitochondrial function, and inhibition of Nrf2, a central regulator of antioxidant-defense gene expression. These pathways provide a coherent rationale for weakened glutathione-dependent defenses, though Nrf2 effects vary by model.

Bottom line

• Aflatoxin: experimental and limited human evidence support oxidative stress and reduced glutathione-dependent antioxidant capacity.
• Ochratoxin A: oxidative stress is supported experimentally; impaired glutathione-dependent capacity is biologically plausible but not directly established in human exposure studies.