Ochratoxin A: the continuing enigma.
The mycotoxin ochratoxin A (OTA) has been linked to the genesis of several disease states in both animals and humans. It has been described as nephrotoxic, carcinogenic, teratogenic, immunotoxic, and hepatotoxic in laboratory and domestic animals, as well as being thought to be the probable causal agent in the development of nephropathies (Balkan Endemic Nephropathy, BEN and Chronic Interstitial Nephropathy, CIN) and urothelial tumors in humans. As a result, several international agencies are currently attempting to define safe legal limits for OTA concentration in foodstuffs (e.g., grain, meat, wine, and coffee), in processed foods, and in animal fodder. In order to achieve this goal, an accurate risk assessment of OTA toxicity including mechanistic and epidemiological studies must be carried out. Ochratoxin has been suggested by various researchers to mediate its toxic effects via induction of apoptosis, disruption of mitochondrial respiration and/or the cytoskeleton, or, indeed, via the generation of DNA adducts. Thus, it is still unclear if the predominant mechanism is of a genotoxic or an epigenetic nature. One aspect that is clear, however, is that the toxicity of OTA is subject to and characterized by large species- and sex-specific differences, as well as an apparently strict structure-activity relationship. These considerations could be crucial in the investigation of OTA-mediated toxicity. Furthermore, the use of appropriate in vivo and in vitro model systems appears to be vital in the generation of relevant experimental data. The intention of this review is to collate and discuss the currently available data on OTA-mediated toxicity with particular focus on their relevance for the in vivo situation, and also to suggest possible future strategies for unlocking the secrets of ochratoxin A.
O'Brien
Evelyn
E
Environmental Toxicology, University of Konstanz, Germany. evelyn.obrien@uni-konstanz.de
Dietrich
Daniel R
DR
D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D018736:DNA Adducts; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007680:Kidney Neoplasms / Q000139:chemically induced; D009793:Ochratoxins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D018384:Oxidative Stress; D018570:Risk Assessment; D013329:Structure-Activity Relationship
D002273:Carcinogens; D018736:DNA Adducts; D009793:Ochratoxins; C025589:ochratoxin A