Gyromitrin, Mushroom Toxin of Gyromitra Spp.

Abstract

Gyromitra esculenta (Persoon ex Fries) mushrooms have been responsible for severe intoxications and even deaths. Clinical data are characterized primarily by vomiting and diarrhea and after a while by jaundice, convulsions and coma. Other Gyromitra species which may be of concern are G. fastigiata and G. gigas; nevertheless, recent advances in chromatography, biochemistry and toxicology have established that other species within the Ascomycetes may also prove toxic. Their toxins, mainly gyromitrin (N-methyl-N-formyl-N-acetyl-hydrazone) and their higher homologues are converted in the milieu of human stomach into N-methyl-N-formylhydrazine (MFH), then into N-methylhydrazine (MH). The toxicity of these latter chemicals, which are mainly hepatotoxic and even carcinogenic, has been established through in vivo and in vitro experiments with cell cultures and biochemical systems. Considering the chemical structure and the reactivity of these natural compounds, chemical and biochemical mechanisms are defined in order to explain their intrinsic biological activity. These findings imply that consumption of G. esculenta could present a carcinogenic as well as an acutely toxic health hazard.

New 2-Methoxy Acetylenic Acids and Pyrazole Alkaloids from the Marine Sponge Cinachyrella sp.

“…A plausible biosynthetic pathway for the isolated pyrazole derivatives 5 – 7 is proposed, which includes the linkage of an acetoacetic acid and an N -acetyl- N -methylhydrazine unit via a Schiff base formation followed by cyclization and dehydration reactions to form 6 . Subsequent reduction of the latter followed by a Schiff base formation with an N -formyl- N -methylhydrazine unit, a natural product originally isolated from the ascomycete fungus Gyromitra esculenta [ 10 ], would finally result in the formation of 5 and 7 , respectively ( Figure 4 ).…”

Human Poisoning from Poisonous Higher Fungi: Focus on Analytical Toxicology and Case Reports in Forensic Toxicology

“…Gyromitrin was finally isolated, synthesized and definitively identified in 1968 by List and Luft as acetaldehyde N -methyl- N -formylhydrazone or gyromitrin (C 4 H 8 N 2 O, M = 100.1) [ 206 , 207 , 208 ]. The hydrolytic cleavage of gyromitrin ( Figure 10 ) leads to the formation of N -methyl- N -formylhydrazine and then methylhydrazine (or monomethylhydrazine, MMH) [ 209 , 210 ], which is used in astronautics as a rocket propellant [ 209 ]. Gyromitrin belongs to the hydrazine family and is volatile, thermosensitive, and very soluble in water [ 207 ].…”

“…N -methyl- N -formylhydrazone and methylhydrazine are known to be hepatotoxic through the mechanism of producing radical species, but they are also known to be carcinogenic in animals [ 209 , 213 ].…”

“…Several studies have been conducted on animals to determine the lethal dose of 50% for gyromitrin and MMH. Patocka et al [ 209 ] reported an oral LD 50 for gyromitrin of 344 mg/kg in mice, 320 mg/kg in rats, 50–70 mg/kg in rabbits, and a resistance of over 400 mg/kg in chickens. In humans, the oral LD 50 is estimated at 20–50 mg/kg in adults and 10–30 mg/kg in children [ 207 ].…”

“…There is no evidence that G. gigas contains gyromitrin. It would appear that a large proportion of the genus Gyromitra contains gyromitrin [ 209 ].…”