European Journal of Biochemistry · 1969 · 41 citations · 3 references
PharmacyPharmacologyToxicologyBiochemical ToxicologyHepatotoxicologyMechanisms Of ToxicityHepatic ToxicityHepatotoxicity MechanismsMechanisms Of Toxic InjuryOrgan ToxicityAmanita Mushroom PoisoningConcentrationGel PhasePaper ChromatographyPoisonous MushroomsRadiotoxicityToxic MetabolitesToxic Mushroom Compounds
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 ([ 3 H]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 [ 3 H]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 [ 3 H]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 [ 3 H]desmethylphalloin; (c) [ 3 H]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 [ 3 H]desmethylphalloin and most probably also phalloidine are not metabolized in the livers of rats and mice.
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MECHANISM OF ACTION OF PHALLOIDIN
L. Fiume · The Lancet · 1965 · 37 citations