The role of bile acids in phalloidin poisoning.

Glycocholate and other bile acids inhibit the response of isolated hepatocytes to phalloidin in a concentration dependent manner. It is suggested that the inhibition is due to a block of phalloidin uptake. This interaction might explain the high specificity of phalloidin for liver tissue.

Decreased phalloidin response, phallotoxin uptake and bile acid transport in hepatocytes prepared from wistar rats treated chronically with diethylnitrosamine.

Isolated hepatocytes prepared from rats pretreated with diethylnitrosamine (0.5 mg/kg DENA/DAY P.O.) are less sensitive to phalloidin poisoning. They take up lower amounts of both phallotoxins and bile acids than controls. The degree of inhibition depends on the period of pretreatment.

Differential effect of raised Mg2+ concentration of K+ ion movement and on swelling in the isolated perfused rat liver poisoned by phalloidin.

The K+ release from the isolated perfused rat liver induced by phalloidin was strongly inhibited on raising the Mg2+ concentration of the perfusion medium from 0.5-40mM while, in contrast, the phalloidin induced swelling of the organ and the vasuolisation of the liver tissue was not affected.

Glucose-6-phosphatase (EC 3.1.3.9) and esterase (EC 3.1.1.1) activities of microsomes prepared from perfused rat livers after partial outflow block or phalloidin poisoning.

Microsomes were prepared from perfused rat livers after different perfusion procedures. The yield of microsomal protein and the kinetic data (Km, Vmax) of glucose-6-phosphatase (3.1.3.9) and esterase (3.1.1.1) activities were analysed in each preparation. No marked differences were detected between conventionally prepared liver microsomes and those from livers perfused 1 hr with an erythrocytes-free medium under the conditions of open outflow. If the outflow pressure was increased artificially, the yield of microsomal protein decreased. The Vmax of both enzymes was markedly increased, whereas the Km values remained unchanged. The same microsomal alterations occurred when perfused rat livers were poisoned with phalloidin in vitro under the condition of open outflow. Our findings indicate that microsomal alterations in livers from poisoned animals might be due to microcirculatory disturbances, and not primary effects of the toxin on the endoplasmatic reticulum.

[Amanita phalloides poisoning in Austria (author's transl)]. / Knollenblätterpilzvergiftungen in Osterreich.

An analysis of 28 cases of amanita phalloides poisoning serves as basis for a discussion of the clinical features and therapeutic problems involved. A critical review of recent experimental investigations in animals points to new possibilities in the treatment of amanita phalloides poisoning.

A concept study on identification and attribution profiling of chemical threat agents using liquid chromatography-mass spectrometry applied to Amanita toxins in food.

Accidental or deliberate poisoning of food is of great national and international concern. Detecting and identifying potentially toxic agents in food is challenging due to their large chemical diversity and the complexity range of food matrices. A methodology is presented whereby toxic agents are identified and further characterized using a two-step approach. First, generic screening is performed by LC/MS/MS to detect toxins based on a list of selected potential chemical threat agents (CTAs). After identifying the CTAs, a second LC/MS analysis is performed applying accurate mass determination and the generation of an attribution profile. To demonstrate the potential of the methodology, toxins from the mushrooms Amanita phalloides and Amanita virosa were analyzed. These mushrooms are known to produce cyclic peptide toxins, which can be grouped into amatoxins, phallotoxins and virotoxins, where α-amanitin and ß-amanitin are regarded as the most potent. To represent a typical complex food sample, mushroom stews containing either A. phalloides or A. virosa were prepared. By combining the screening method with accurate mass analysis, the attribution profile for the identified toxins and related components in each stew was established and used to identify the mushroom species in question. In addition, the analytical data was consistent with the fact that the A. virosa specimens used in this study were of European origin. This adds an important piece of information that enables geographic attribution and strengthens the attribution profile.

[Phalloidin syndrome: role of Elisa-based assay for the detection of alpha- and gamma-amanitins in urine. Preliminary results]. / Syndrome phalloïdien: quelle est la place du dosage des alpha- et gamma-amanitines par ELISA (Bühlmann)? Résultats préliminaires.

UNLABELLED: After consumption of mushrooms containing amatoxins (Amanita, Lepiota, and Galerina species), symptoms usually develop after a long delay (>6 h). Initial symptoms start as severe gastroenteritis, progressing to liver failure and possibly death as a result of hepatic coma. Since the survival rate of poisoned patients is claimed to depend on the time of beginning of efficient treatment, fast and reliable assays for amatoxins in biological fluids are essential. Described analytical methods for amatoxins include high performance liquid chromatography and radioimmunoassay (RIA). Recently, a new enzyme-linked immunosorbent assay (Bühlmann Amanitin ELISA kit) has been introduced as an alternative method to RIA. This ELISA-based assay offers several advantages: no complex extraction procedure is required (vs. HPLC) and no safety precautions concerning radioactivity have to be taken (vs. RIA). From August 2004 to October 2005, a pilot study was performed to test the practicability and the clinical utility of this method in emergency situations. RESULTS: ten urines, 9 serums and 1 faeces from 10 patients suffering from acute gastroenteritis after mushroom ingestions (7 contaminated meals) were analyzed. Definitive diagnosis of amatoxin poisoning was made in 4 cases (3 contaminated meals) on the basis of the anamnesis, laboratory results, and clinical course. A patient developed a severe amatoxin poisoning with urinary amanitins level < 1.5 microg/L (urines were collected more than 72 h after mushroom ingestion). Two patients were paucisymptomatic with urinary amanitins levels >10 microg/L (urines were collected before the 36th hour). CONCLUSION: Urine is the sample of choice for the determination of amatoxins. The most critical factor to invalidate the usefulness of this analysis is time. After 36 h, the sensitivity is unreliable.

[Haemoperfusion with activated charcoal and ion exchanger in phalloidin intoxicated rats (author's transl)]. / Hämoperfusion mit Aktivkohle und Ionenaustauscher bei phalloidin-vergifteten Ratten

Amberlite-XAD-4 and activated charcoal haemoperfusion permit a considerable increase in 14C-methyl-phalloin elimination in vitro which surpasses the effect of haemodialysis treatment. However, in the in-vivo experiment using phalloidin intoxicated rats (1.5 or 2.0 mg/kg i.v.) prolongation of the survival period could not be attained 0y haemoperfusion.

Protection by phalloidin against lethal doses of phalloidin.

Tolerated doses of phalloidin, a toxin from the mushroom Amanita phalloides, protect mice against lethal doses of phalloidin. Resistance is conferred by the 1/10 LD95 of phalloidin and sets in at about 8 hours after the pretreatment.

[Glucose tolerance and insulin sensitivity of rats poisoned with amanita-phalloidines]. / Tolerantnost' k gliukoze i chuvstvitel'nost' k insulinu u krys, otravlennykh amanita-falloidinami.

The effect Amanita phalloides on glucose tolerance and insuline sensitivity was studied. Amanita phalloides toxins were injected to albino male rats intraperitoneally in a dose of DL50. Amanita phalloides proved to cause disturbance of glucose tolerance, increased tissue glucose utilization, and enhanced the organism insuline sensitivity. The mentioned effects result from a decrease of insuline-inactivating capacity of the liver and from enhanced function of the insuline apparatus of the pancreas.

Acute phalloidin poisoning in dogs.

The acute toxic effects of phalloidin, a toxin from the green deathcup, Amanita phalloides, were tested in dogs. No fatalities occurred following intravenous injection; however, the biochemical parameters GPT, GOT, alkaline phosphatase, and total bilirubin yielded pathological values. Histologically the liver parenchyma revealed hemorrhagic necrosis and peliosis-like changes with penetration of red blood cells into hepatocytes.

The toxicology of Amanita virosa: the destroying angel.

This paper examines the biology and medical consequences of ingesting the potentially lethal poisonous mushroom, Amanita virosa, the Destroying Angel. The fungus, its structure, distribution and toxic components are described. Symptoms of human poisoning by A. virosa are described, following the order of Homeopathic Repertories. Laboratory values for comparison with normal values of haematology, biochemistry and urine analyses are given.

[Cholinesterase activity as a prognostic test in phalloidine mushroom poisoning]. / Kholinesteraznata aktivnost kato prognostichen test pri faloidna gubna intoksikatsiia.

The phalloidine mushroom poisoning is an exogenic intoxication with specific action of the mushroom toxins on the liver and its functions. The dynamic follow up of serum cholinesterase activity in patients with phalloidine intoxication revealed that it was significantly decreased in the patients who died in comparison to those who survived. In the patients who survived and recovered the serum cholinesterase was moderately decreased and later increased. As a protein product synthesized in the liver the serum cholinesterase is a good marker of the protein-synthesizing function of the liver in patients with phalloidine intoxication and may be used as a prognostic test for its outcome.

[Anti-phalloidine activity of the silymarins silybine and disilybine]. / Zur anti-phalloidin-Aktivität der Silymarine Silybin und Disilybin

Originating from silybin, a phenylchromanone from Silybum marianum (L.) Gaertn., a dimer -- disilybin -- was prepared. Disilybin exhibits a phalloidin antagonistic activity at least 10 times that of silybin with regards to a dose of the same weight.

[Hemo and cross dialysis treatment in phalloidin intoxication in the waking rat]. / Hämo- und Cross-Dialysebehandlung der Phalloidin-Intoxikation an der wachen Ratte

In vitro 14C-Methyl-Phalloidin is found to be well dialysable; in vivo dialysis is less effective. In rats the application of 2 mg/kg Phalloidin i.v. led to death after 106 minutes on the average. Hemodialysis with electrolyte-glucose solution or with plasma protein solution immediately started after Phalloidin injection did not alter the survival time significantly. Only a group of rats which was cross dialysed immediately after intoxication showed a statistically insignificant prolongation of survival time of 16 minutes. The histomorphological findings of the liver were similar in all groups. We found a phalloidinic vacuolisation of the cytoplasm of the lobular periphery, hemorrhagic necrosis and also fatty changes in the periphery of the lobule with small fat droplets and pycnosis of nuclei. Specific Phalloidin effects, too, were found in the liver of both animals used in cross-dialysis, which proves that Phalloidin is dialysable by this method.

[Somatotropin, antidot against phalloidin (author's transl)]. / Somatotropin, Antidot gegen Phalloidin.

1. Somatotropin protects rats against a lethal dose of phalloidin (1.3 mg/kg). 2. Scanning electron microscopy has shown that 2 hours after phalloidin injection the liver from a somatotropin-pretreated rat is not significantly different to that from an untreated rat. Phalloidin alone caused complete destruction of the structure of the liver lobules. 3. Somatotropin does not prevent phalloidin uptake by the liver but slows down elimination. 4. The findings are discussed with respect to their therapeutic possibilities as somatropin protects rats against death also after phalloidin poisoning.