Ochratoxin A in food and feed: occurrence, legislation and mode of action.
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Ochratoxins, of which ochratoxin A (OA) is the most prevalent, are secondary fungal metabolites of some toxigenic species of Aspergillus and Penicillium. OA has been shown to be nephrotoxic, hepatotoxic, teratogenic, carcinogenic and immunosuppressive. The natural occurrence of OA in food and feed stuffs is widespread, especially in temperate areas such as Canada, Denmark, Germany, Sweden and the United Kingdom, and detectable amounts were even found in randomly collected human milk samples in Germany, Sweden and Italy. Of greatest concern in humans is its implicated role in an irreversible and fatal kidney disease referred to as Balkan Endemic Nephropathy. The mean dietary intake for humans in the European Union was found to be in the range of 1 to 2 ng/kg bw/day. Compared with the Provisional Tolerable Daily Intake (PTDI) proposed by the WHO of 16 ng OA/kg bw/day for humans, the average OA intake in Europe seems to be rather low. The main contributor to the OA intake in humans are cereals and cereal products, other possible contributors are coffee, beer, pork, products containing pig blood/plasma, pulses and spices. Only very few countries have regulations for OA in food and feed products. Based on the current literature, the mechanisms involved in the toxicity of OA indicate three major effects: (1) inhibition of mitochondrial respiration correlated with a depletion of ATP; (2) inhibition of tRNA-synthetase accompanied by a reduced protein synthesis; and (3) enhanced lipid peroxidation. Generation of free radicals and lipid peroxidation as an important mode of action of OA in vitro and in vivo is discussed in detail, as well as counteracting effects of dietary antioxidants.