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Review
. 2016 Jul 4;8(7):191.
doi: 10.3390/toxins8070191.

Ochratoxin A: 50 Years of Research

Frantisek Malir  1 , Vladimir Ostry  2 , Annie Pfohl-Leszkowicz  3 , Jan Malir  4 , Jakub Toman  5
Affiliations
Review

Ochratoxin A: 50 Years of Research

Frantisek Malir et al. Toxins (Basel). .

Abstract

Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but can also damage poultries. Humans exposed to OTA can develop (notably by inhalation in the development of acute renal failure within 24 h) a range of chronic disorders such as upper urothelial carcinoma. OTA plays the main role in the pathogenesis of some renal diseases including Balkan endemic nephropathy, kidney tumors occurring in certain endemic regions of the Balkan Peninsula, and chronic interstitial nephropathy occurring in Northern African countries and likely in other parts of the world. OTA leads to DNA adduct formation, which is known for its genotoxicity and carcinogenicity. The present article discusses how renal carcinogenicity and nephrotoxicity cause both oxidative stress and direct genotoxicity. Careful analyses of the data show that OTA carcinogenic effects are due to combined direct and indirect mechanisms (e.g., genotoxicity, oxidative stress, epigenetic factors). Altogether this provides strong evidence that OTA carcinogenicity can also occur in humans.

Keywords: Balkan endemic nephropathy; biomarkers; carcinogenicity; feed; food; microfungi; ochratoxin A; toxicity; urothelial cancer.

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Figures

Figure 1
Figure 1
The milestones in ochratoxin A (OTA) research in years 1965–1990.
Figure 2
Figure 2
The milestones in OTA research in years 1991–2000.
Figure 3
Figure 3
The milestones in OTA research in years 2000–2015.
Figure 4
Figure 4
Structural formula of OTA.
Figure 5
Figure 5
The milestones in evolution of legal regulation of OTA in years 1965–2015.
Figure 6
Figure 6
Summary of biochemical effects of OTA. Explanations: OTA: Ochratoxin A; OTHQ: Hydroxyl quinone ochratoxin; OTB: Dechlorinated ochratoxin; LIPOX: Lipoperoxidation; Nox: Nitrogen oxide; ROS: Reactive oxygen species.
Figure 7
Figure 7
Metabolic activation of ochratoxin leading to DNA adducts. OTA: Ochratoxin A; OTHQ: Hydroxyl quinone ochratoxin; OTQ: Quinone ochratoxin; OTB: Dechlorinated ochratoxin; GSH: Reduced glutathione; GS: Oxidized glutathione; dG-OTA: Guanine OTA adduct.
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