Mycotoxin amanitin

The statins, lovastatin (L), simvastatin (S), pravastatin (P), fluvastatin (F), cerivastatin, and atorvastatin, inhibit HMG CoA reductase. The active group of L, S, P, and F (or their metabolites) resembles that of the physiological substrate of the enzyme (A). L and S are lactones that are rapidly absorbed by the enteral route, subjected to extensive first-pass extraction in the liver, and there hydrolyzed into active metabolites. P and F represent the active form and, as acids, are actively transported by a specific anion carrier that moves bile acids from blood into liver and also mediates the selective hepatic uptake of the mycotoxin, amanitin (A), Atorvastatin has the longest duration of action. 

Amanita phalloides Mycotoxins, especially a-amatoxin, are extremely hepatotoxic as a result of the inhibition of mRNA polymerase B and the blocking of RNA synthesis. The lethal dose is approx. 0.1 mg amatoxin/kg BW (1-3 fungi = 10-50 g), depending on the patient s age and state of health as well as the respective degree of intestinal absorption and diffusion in the tissue. The heat-resistant mycotoxins (amanitines) are capable of enterohepatic recirculation, (s. pp 383, 571)... 

The mode of action of mushroom-produced mycotoxins varies considerably. Alpha amanitin, amatoxin produced by some species of Amanita, is a class A poison that acts by inhibiting a critical nuclear polymerase that enables the cell to make protein. Once the function of this RNA polymerase is curtailed, basic life processes cease. Attempts to kill alpha amanitin with antibodies have proven to be even more harmful to patients than the poison itself. Most forms of mushroom poisoning can be treated with rapid lavage (induced vomiting) or medically approved ingestion of charcoal to absorb the toxin before it is absorbed into the stomach. 

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