Cyclopeptides: gastrointestinal, renal, and hepatic effects

Amatoxins inhibit one of two mammalian nuclear RNA poly-merase B forms, which are involved in the transcription of DNA to messenger RNA. They therefore cause inhibition of protein synthesis at the ribosomes.^2–5

Amanita and Galerina species are most commonly involved. The Galerina mushrooms are small, dark brown, and grow on wood. Amanita mushrooms come in a variety of colors and have a vulva, an annulus, and universal veil remnants. The primary target organs of the cyclopeptide toxins are the gastrointestinal tract, kidney, and liver. After ingestion of these toxins by a human, there is usually a latent period during which little happens for several hours. The patient then starts to vomit and may have diarrhea and intense abdominal pain for several hours.^7–9 The vomiting then subsides, and the patient may seem almost normal. During the next several days, the toxins cause hepatic and renal failure. If the dose has been high enough, the patient dies in the following few days. During this time hepatic enzymes are elevated, and the patient may be jaundiced and anuric from the toxins or from hypovolemia. Tachycardia, acid-base abnormalities, dehydration, hypotension, electrolyte abnormalities, hepatic coma, coagulation abnormalities, hypoglycemia, and shock may occur.^10–12 Laboratory tests may show elevations in prothrombin time, Quick’s test values (a measure of plasma prothrombin), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), serum bilirubin, and creatinine.^6,13 Amanita smithiana, usually found in the northwestern states, can cause renal tubular necrosis with fewer hepatic signs. Although amatoxins can be detected in the blood using a radioimmunoassay, this test is seldom helpful because the toxins disappear from the blood fairly quickly, 2 to 36 hours in humans.

Several treatments have been tried in humans with moderate success. Decontamination of the gastrointestinal tract is a good idea if the ingestion has occurred within the last few hours. Emesis and/or lavage, along with administration of activated charcoal, may be used. Multiple doses of charcoal, given several hours apart, have been useful in humans because of enterohepatic circulation.¹⁴ Good supportive care is crucial, with observation and treatment of renal failure, hepatic coma, acid-base abnormalities, bleeding, hypoglycemia, or dehydration.¹⁵ Coagulopathies may require injections of vitamin K_1. Blood transfusions may be necessary. Liver transplants have been done in humans but would be rare in animals.

Thioctic acid was once recommended, but it was difficult to obtain and had mixed success. Penicillin G, in human doses of 300,000 to 40 million U/day, has been tried and seems to be of some benefit if given within a few hours of ingestion.^7,16,17 Animal experiments seem to indicate that penicillin G reduces hepatic uptake of the toxin. Another agent used is silymarin, derived from the milk thistle Silybum marianum.^7,18–25 The flavonolignans in silymarin have been found to be protective in animals. Silymarin is thought to be a free radical scavenger and an inhibitor of the penetration of the amatoxins into liver cells. Human doses are 20 to 50 mg/kg/day given intravenously (not available in the United States) or 1.4 to 4.2 g/day orally.²⁶ When using herbal milk thistle, the concentration of silymarin should be determined from the label and the amount needed for a 1.4 to 4.2 g dose calculated from that. The drugs are usually given for about 4 to 5 days. Often penicillin G and silymarin are used together. Forced diuresis has also been tried with some success.^15,27 An antibody against amatoxin has been developed in rabbits but is experimental only.²⁸

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