Is that mushroom toxic? (Proceedings) - Veterinary Healthcare
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Is that mushroom toxic? (Proceedings)


CVC IN SAN DIEGO PROCEEDINGS


Human and canine exposure to potentially toxic mushrooms is relatively common. In 2007, the American Association of Poison Control Centers (AAPCC) reported a total of ~ 7700 calls related to mushroom exposure. The difficulty for the clinician is that rapid and proper identification of ingested mushrooms occurs infrequently. For example, a specific mushroom was not identified in ~ 84% of the calls to the AAPCC. Fortunately, in the majority of human cases, adverse effects are uncommon. No human fatalities were reported in 2007 and there were only 35 cases in which a major adverse effect occurred. Presumably, this is also true for animal exposures, although good data are lacking. While most mushroom ingestions are benign, some mushrooms contain hepatotoxic cyclopeptides that, when ingested, cause life-threatening effects. Worldwide most human fatalities following mushroom ingestion are associated with those containing hepatotoxic cyclopeptides.

There are ten groups of toxins that have been identified in mushrooms: the aforementioned cyclopeptides, gyromitrin, muscarine, coprine, ibotenic acid and muscimol, psilocybin, general GI irritants, orellinine, allenic norleucine and myotoxins. This discussion will focus on the cyclopeptide hepatotoxins.

Occurrence


Fig. 1: Approximate U.S. distribution of A. ocreata.
Hepatotoxic, cyclopeptide-containing species include the Amanita spp. (~ 9 species), Galerina spp. (~ 9 species) and Lepiota spp. (up to 24 species). In North America, Amanita spp., especially A. phalloides, (death cap or death angel) are most commonly implicated in causing significant disease in humans, although in Eastern Europe, Galerina sulpices is considered to be the species most often associated with mortality. Data specific to animals is lacking. However, based upon a series of documented cases in our laboratory, Amanita spp. (A. phalloides and A. ocreata) were the most commonly involved in intoxications. Both species are common in California and are associated with Quercus agrifolia or coast liveoak, but are found in other regions of the U.S. The distribution of A. ocreata in North America is provided in Figure 1.


Fig. 2: α-amantin, a bicyclic octapeptide.
Hepatotoxic mushrooms contain three groups of cyclopeptides that vary in toxicity. These include the bicyclic octapeptide amatoxins and phallotoxins and the monocyclic heptapeptide virotoxins. Phallotoxins and verotoxins are not believed to have significant oral toxicity. Thus, the amatoxins are responsible for causing cellular damage. Amatoxins include α-, β-, γ-, and ε-amanitins, amanin, amanullin and proamanullin (see Figure 2 for α-amanitin structure). α- and β-amatoxin are present in approximately equal concentrations and account for over 90% of the amatoxin content of the mushroom.

α- and β-amantins are the most toxic amatoxins, with LD50s in mice of 0.1 to 0.75 mg/kg and 0.2 to 0.4 mg/kg b.w., respectively. An oral LD50 in dogs of methyl-γ-amanitin has been estimated to be 0.5 mg/kg body weight. Approximately 1.5 to 2.5 mg of total amanitin is present in 1 g of dry A. phalloides. Thus, a 20 g mushroom contains a potentially lethal dose (0.1 mg/kg or greater) for a human or a 10 kg dog. Interestingly, rats are resistant to the toxic effects of amanitins.

Toxicokinetics of Amanitins

The bioavailability of amanitins appears to vary with species with decreasing bioavailability reported for humans, dogs and mice and rabbits. Following systemic absorption, it is believed that hepatocytes take up α-amanitin via a sodium dependent, bile acid transporter or via an organic anion-transporting polypeptide.

α-amanitin has a low volume of distribution, no known plasma protein binding or liver metabolism and high renal clearance. After oral ingestion of A. phalloides in humans, α- and β-amanitins were detected in plasma for up to 36 hours and in urine for up to 72 hours post-exposure. In contrast, the half-life of amantins is short (25 to 50 minutes) in dogs given amanitins IV; they were detectable in plasma for only 4 to 6 hours. Amanitins have been detected in human liver and kidney tissue for up to 22 days post- exposure, with the highest concentrations detected in kidney tissue.


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