Metabolic activation and detoxification of mycotoxins

Of the metabolites of aflatoxin B₁ formed by liver enzymes, 3 are specially important. 1. Aflatoxin M₁ is a potential environmental health hazard. Thus, when livestock have access to contaminated feedstuffs, residues of this toxic metabolite may accumulate in animal products used for human food. 2. Although aflatoxin hemiacetal, B2a, is virtually non-toxic when fed to experimental animals, on being formed in the liver cell it probably combines indiscriminately with amino-acids, peptides and proteins, interferes with many facets of liver metabolism leading to cell necrosis and may thus be regarded as the « acute toxin ». 3. Aflatoxin B₁ is also activated by liver microsomal enzymes in vitro to form a mutagenic metabolite which is probably the 2,3-epoxide and which may be the ultimate carcinogen. Sterigmatocystin is structurally similar to aflatoxin B₁ and also requires activation, possibly to the epoxide, before it is mutagenic in bacterial test systems. However, liver preparations capable of converting aflatoxin to its hemiacetal do not transform sterigmatocystin into the corresponding metabolite. This suggests that, besides the epoxide, the parent toxin is the only active molecule and may explain why sterigmatocystin is about 125 times less toxic than aflatoxin. Ochratoxin A itself is probably the only active molecular form and in the rat and pig it is absorbed as such in the upper gastro-intestinal tract. Hydrolysis to the non-toxic ochratoxin takes place in the small intestine. Ochratoxin B is less readily absorbed and more easily hydrolysed. Trichothecenes are metabolised in vitro by liver enzymes with loss of the 12,13-epoxide function as judged by the Rat dermal bioassay. These enzymes are stimulated in the duck and rat by phenobarbital pretreatment and one such enzyme has been identified as glutathione-S-epoxide transferase. A preparation of the latter enzyme has been used as the reagent in a proposed enzymic assay method for trichothecenes in extracts of animal feedstuffs.