Do ochratoxin A and aflatoxins cause oxidative stress and mitochondrial dysfunction?

Ochratoxin A (OTA) and aflatoxins are foodborne mycotoxins with experimentally established oxidative and mitochondrial toxicity. Their principal organ associations differ: OTA is predominantly nephrotoxic, whereas aflatoxins—especially aflatoxin B1 (AFB1)—have their clearest human consequence in the liver.

Experimental and mechanistic evidence

• OTA increases reactive oxygen species (ROS) in renal mesangial cells and, in HEK293 cells, ROS accompanies mitochondrial membrane-potential loss and apoptosis. OTA-exposed zebrafish embryos show reduced ATP and NADH, consistent with impaired energy metabolism. In renal tubular models, impaired mitochondrial respiration can precede cell death.
• AFB1 increases mitochondrial ROS, lowers mitochondrial membrane potential, alters antioxidant-pathway signaling, and induces apoptosis in primary hepatocytes. Experimental literature also describes respiratory-chain impairment, reduced ATP production, and permeability-transition-associated injury. These findings are strongest for AFB1 rather than every aflatoxin congener.

Organ-specific toxicity

• OTA is a well-supported renal toxicant: it accumulates in kidney tissue, with renal tubular injury and dose- and duration-related renal damage in animal studies. JECFA’s provisional tolerable weekly intake of 100 ng/kg body weight/week was based on pig kidney toxicity. Direct causal evidence for chronic kidney disease in humans at usual exposures remains insufficient.
• Aflatoxins cause liver cancer in humans. In a Taiwanese prospective study, higher urinary AFB1 metabolites predicted hepatocellular carcinoma (OR 1.76, 95% CI 1.18–2.58); AFB1–albumin adducts were similarly associated (OR 1.54, 1.01–2.36). Hepatitis B and high aflatoxin exposure together were associated with OR 15.13.

Carcinogenic mechanism

• Hepatic cytochrome P450 converts AFB1 to an 8,9-exo-epoxide that forms DNA adducts, including AFB1-N7-guanine, promoting mutations such as the characteristic TP53 codon-249 G-to-T transversion.

Bottom line

• The claim is supported: both toxins can drive oxidative and mitochondrial injury experimentally; OTA is particularly linked to kidney toxicity, while aflatoxins have a definitive liver-cancer association, with AFB1’s DNA-adduct-mediated mutagenesis providing the strongest causal mechanism.