Can ochratoxin A produce oxidative stress and neuroinflammatory effects in experimental brain models?

Ochratoxin A (OTA) is a foodborne mycotoxin. Experimental neural models consistently show oxidative and inflammatory responses after exposure, although these findings do not establish equivalent effects or neurological risk at ordinary human dietary exposures.

Experimental neurotoxicity evidence

• Oxidative stress: Human astrocytes exposed to OTA for 24 hours showed dose-dependent increases in reactive oxygen species (ROS). Across neural culture and mouse models, reported findings include ROS generation, lipid peroxidation, impaired antioxidant defenses, and oxidative injury.
• Mitochondrial and genomic injury: Neural cultures show mitochondrial membrane-potential loss and mitochondrial injury. In mice, acute exposure increased oxidative stress and oxidative DNA damage across multiple brain regions.
• Neuroinflammation: OTA directly activates inflammatory signaling in glia. In BV-2 microglia, it increased IL-6, TNF-α, IL-1β, and inducible nitric-oxide synthase (iNOS), alongside greater IL-6 and nitric-oxide release. Human-derived microglia released IL-1β, IL-18, and CXCL8 after exposure. Repeated mouse exposure produced an M1-like pro-inflammatory microglial phenotype.

Mechanistic and neuropathological context

• Oxidative and inflammatory findings are biologically coherent but should not be interpreted as proving one linear pathway in which ROS necessarily drives inflammation.
• Additional mouse findings include reduced striatal dopamine after acute exposure and dose-related reductions in hippocampal astrocytes and neurons after repeated exposure, consistent with broader neural vulnerability.
• Brain exposure may be constrained by blood–brain-barrier efflux, complicating translation from experimental dosing to real-world exposure.

Bottom line

• OTA can produce oxidative stress, mitochondrial dysfunction, oxidative DNA damage, and pro-inflammatory glial responses in experimental brain models. The evidence is strong for these model-system effects, but it does not demonstrate comparable brain injury, neuroinflammation, or neurologic disease in humans at typical dietary exposure levels.