Page 1027 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Mushroom Toxins Chapter | 67 959

VetBooks.ir HYDRAZINES (GABA) synthesis and an increase in glutamic acid con-
centrations. Based on a study of mice in which GABA con-
Gyromitra species are members of the false morel family,
centrations in the brain were not significantly decreased
and Helvellaceae are usually found under conifers,
after methylhydrazine exposure (Maynert and Kaji, 1962),
aspens, and sometimes around melting snow banks. The
other mechanisms have been proposed. In addition to the
species most commonly associated with poisoning and
gastrointestinal irritation and neurotoxicity, liver and renal
studied in most detail is Gyromitra esculenta, but the tox-
failure as well as hemolysis has been described. N-methyl-
ins have been found in other species of Helvellaceae
N-formylhydrazine inhibits cytochrome P450 and
(Viernstein et al., 1980), including Gyromitra gigas,
glutathione-metabolizing enzymes (Braun et al., 1979), and
Gyromitra fastigiata, Gyromitra infula, Helvella crispa,
it can cause liver necrosis. However, the highly reactive
and Helvella lacunose. The toxins associated with false
metabolites, such as methyl cations, generated in the liver
morel poisoning are hydrazine analogs. The toxins are
may significantly contribute to the hepatic injury.
heat labile, volatile, and water soluble (Michelot and
Furthermore, the hydrazine analogs present in false morels
Toth, 1991). The process of boiling and drying decreases,
are carcinogenic in laboratory animals (Toth and Gannett,
but does not completely eliminate, the toxin concentra-
1994). Only one case report exists in the veterinary litera-
tions (Pyysalo, 1976). People who eat only a few of the
ture. A 10-week-old dog vomited 2 or 3 h after chewing on
cooked mushrooms may ingest sufficiently detoxified
a mushroom later identified as G. esculenta (Bernard,
amounts so as to remain symptom free. This has caused
1979). Six hours postingestion, the dog was lethargic,
misunderstandings among people with regard to the
became comatose, and died 30 min later. Histopathological
potential lethality of these mushrooms. Animals generally
findings included renal tubulonephrosis, periascinar hepatic
eat raw mushrooms; therefore, any exposure to these
degeneration, and erythrophagocytosis.
mushrooms can result in serious morbidity and mortality.
Poisoning by some species of Helvella, Verpa, Morchella,
Peziza, Disciotis, and Sarcosphaera closely resembles the Toxicity
syndrome caused by gyromitrin. It has been speculated
In humans, there seems to be great individual variability
that these mushrooms also contain hydrazines, although
with regard to the toxicity of false morel. In mice, the
analysis has yet to confirm the presence of these toxins
oral LD 50 s of gyromitrin, N-methyl-N-formylhydrazine,
(Lincoff and Mitchel, 1977b).
and monomethylhydrazine are 344, 118, and 33 mg/kg,
respectively (Wright et al., 1978). In humans, the esti-
Pharmacokinetics/Toxicokinetics mated lethal dose of gyromitrin is 20 50 mg/kg for
adults and 10 30 mg/kg for children (Schmidlin-
There is very limited information available. Toxicosis can Meszaros, 1974). Toxicity information for dogs or cats
result after oral and inhalation exposure. Ingestion of does not exist. Gyromitrin concentrations in fresh
gyromitrin (acetaldehyde N-methyl N-formylhydrazone)- G. esculenta are estimated to be 0.12% 0.16%.
containing mushrooms results in the hydrolysis of gyro-
mitrin to N-methyl-N-formylhydrazine, which is further Treatment
metabolized to monomethylhydrazine. The degree of
hydrolysis is dependent on the pH in the stomach, but it is Most humans only develop mild gastrointestinal symp-
not complete (Wright et al., 1978). Inhalation of the toms and recover fully within several days after exposure.
fumes during the cooking process can also result in poi- Management is principally supportive. Early decontami-
soning. Once hydrazines reach the liver, they are further nation is often not possible because of the delayed onset
metabolized to reactive intermediates, such as methyl of clinical signs. Administration of activated charcoal has
cations and free methyl radicals (Gannett et al., 1991). been recommended, although efficacy data do not exist.
Correction of fluid and electrolytes is an important mea-
sure along with the administration of pyridoxine. The
Mechanism of Action
recommended dose in humans is 25 mg/kg i.v. over
Gyromitrin is considered a gastrointestinal irritant leading 15 30 min. The dosing can be repeated but should not
to vomiting, abdominal pain, and diarrhea 6 12 h after exceed more than 20 g/day. Although pyridoxine can suc-
ingestion (Coulet and Guillot, 1982). The principal toxin cessfully control seizure activity, it has no benefit in pre-
responsible for convulsions seen in severe cases is mono- venting liver injury. In dogs, pyridoxine has been used
methylhydrazine, which inhibits pyridoxal phosphokinase successfully for nonmushroom toxin induced seizure
0
resulting in decreased pyridoxal 5 -phosphate concentra- activity. It can be used alone or in combination with diaz-
tions (Lheureux et al., 2005). Depletion of pyridoxal epam, but combination therapy has better efficacy than
0
5 -phosphate leads to decreased γ-aminobutyric acid pyridoxine alone (Villar et al., 1995). The dose for dogs