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Abstract

Various observations cited at the beginning of this paper and in the Discussion suggested that phalloidine, a poisonous constituent of the green mushroom Amanita phalloides, would not be toxic by itself, but would be rendered toxic previously in the liver. Using a tritiated toxic derivative of phalloidine ([3H]desmethylphalloin) we found that: (a) in rats, 60% of the administered substance are excreted unchanged in the urine within the first day. A second radioactive substance of low concentration, moving more slowly in paper chromatography, turned out as a product of the self-degradation of [3H]desmethylphalloin; (b) respectively 98% and 99,9% of the radioactivity were extracted with methanol from homogenates of livers of rats or mice which had received [3H]desmethylphalloin 1 to 2 hours before. Aqueous homogenates of liver of poisened rats also contained radioactivity firmly bound to a high molecular weight substance, as shown by gel chromatography. The radioactive substance was totally removed from the carrier, presumably ribosomal material, by adding methanol, and was identified as [3H]desmethylphalloin; (c) [3H]desmethylphalloin was not metabolized on incubation with oxygen and rat liver ribosomes in a NADPH-regenerating system. A radioactive substance extracted from liver microsomes of a poisoned rat also proved to be original toxin. As a result of these experiments it can be concluded that [3H]desmethylphalloin and most probably also phalloidine are not metabolized in the livers of rats and mice.