ファロイジン

PRETREATMENT WITH RIFAMPICIN (100 OR 300 MG/KG, ORAL) PROTECTED MICE AGAINST THE TOXICITY OF PHALLOIDIN (3 MG/KG, IP) AS REFLECTED BY THE DECREASE IN THE MORTALITY RATE.

IN MICE, THE ACUTE HEMORRHAGIC NECROSIS OF THE LIVER INDUCED BY PHALLOIDIN WAS PREVENTED BY TREATMENT WITH SILYBIN, A PLANT COMPOUND ISOLATED FROM SILYBUM MARIANUM. PRETREATMENT WITH A SINGLE DOSE OF SILYBIN COMPLETELY ABOLISHED THE MORPHOLOGIC CHANGES INDUCED BY THE TOXIN, AND SIGNIFICANTLY DECREASED THE ACTIVITIES OF SERUM ENZYMES.

It binds actin, preventing its depolymerization and poisoning the cell. Phalloidin binds specifically at the interface between F-actin subunits, locking adjacent subunits together. Phalloidin, a bicyclic heptapeptide, binds to actin filaments much more tightly than to actin monomers, leading to a decrease in the rate constant for the dissociation of actin subunits from filament ends, which essentially stabilizes actin filaments through the prevention of filament depolymerization. Moreover, phalloidin is found to inhibit the ATP hydrolysis activity of F-actin (L1183).

Hypovolemic shock; Gastrointestinal symptoms occur after a latent period and include abdominal pain, vomiting, and watery diarrhea. Neurologic symptoms are related to hepatic failure and may include encephalopathy, somnolence, confusion, coma and seizures (L1160).

THE MOST SERIOUS FORM OF MYCETISMUS IS PRODUCED BY GALERINA SPECIES, AMANITA VERNA, AMANITA VIROSA, AND AMANITA PHALLOIDES, WHICH ARE FAIRLY COMMON IN BOTH NORTH AMERICA AND EUROPE. THESE SPECIES ACCOUNT FOR 90% OF ALL FATAL CASES. THE PRINCIPAL TOXINS ARE THE PHALLOIDINS, A GROUP OF CYCLIC HEPTAPEPTIDES THAT APPEAR TO INHIBIT PROTEIN SYNTHESIS, AND THE AMANITINS, WHICH INHIBIT RNA POLYMERASE II AND HENCE INTERFERE WITH THE SYNTHESIS OF MESSENGER RNA. THE TOXINS DISRUPT HEPATIC CELL MEMBRANES AND THE STRUCTURE OF THE ENDOPLASMIC RETICULUM. /PHALLOIDINS/

THE PHALLOTOXINS ARE SOMETIMES SAID TO BE RESPONSIBLE FOR...INITIAL GASTROENTERITIS /OF MUSHROOM POISONING/, BUT PHALLOIDIN ALSO CONTRIBUTES TO THE LIVER LESION BY PROMPTLY AND SPECIFICALLY DAMAGING THE ENDOPLASMIC RETICULUM.

THE PHALLOTOXINS (WHICH INCLUDE PHALLOIDIN) POSSESS A COMMON CYCLIC HEPTAPEPTIDE SKELETON WITH SOME UNUSUAL AMINO ACIDS. AT LEAST IN THE CASE OF PHALLOIDIN, WHICH MAY OR MAY NOT HAVE TO BE ALTERED CHEMICALLY BY THE LIVER BEFORE IT ACQUIRES ITS CHARACTERISTIC ABILITY TO INJURE THAT ORGAN, CYTOTOXICITY IS ASSOCIATED WITH A THIOETHER LINKAGE BETWEEN CYSTEINE AND TRYPTOPHAN IN THE TOXIN MOLECULE.

AMANITA PHALLOIDES CONTAINS TOXIC POLYPEPTIDES INCLUDING PHALLOIDINE AND ALPHA- AND BETA AMANITINE. PHALLOIDINE CAUSES DEGENERATIVE CHANGES IN THE KIDNEY AND LIVER.

IN MICE, CENTRAL NERVOUS EXCITATION, PARALYSIS, AND DEATH FOLLOWED IP INJECTIONS OF PHALLOIDIN.

MICROSCOPIC AND IMMUNOFLUORESCENCE TECHNIQUES WERE USED TO EXAMINE THE LIVER OF RATS INJECTED IV WITH PHALLOIDIN (1-5 MUG/G). PHALLOIDIN AFFECTED PRIMARILY THE PLASMA MEMBRANE OF HEPATOCYTES AND INTERACTED WITH THE ACTIN-LIKE PROTEIN LOCATED CLOSE TO THE INNER LEAFLET OF THE MEMBRANE, CAUSING A MARKED INCREASE IN ACTIN FILAMENTS IN THE CELL.

CHOLESTASIS WITH HYPERBILIRUBINEMIA WAS INDUCED IN FEMALE BUT NOT MALE, SPRAGUE-DAWLEY RATS BY DAILY TREATMENT WITH PHALLOIDIN FOR 7 DAYS. INCREASES IN SERUM DIRECT BILIRUBIN LEVEL AND ALKALINE PHOSPHATASE ACTIVITY WERE OBSERVED CONCOMITANTLY WITH DIMINISHED BILE FLOW AND A DECREASED OUTPUT OF BILE ACID AND CHOLESTEROL. LIGHT MICROSCOPY OF THE LIVER REVEALED PROLIFERATED BILE DUCTULES AND ENHANCED MITOSIS OF HEPATOCYTES.

NO FATALITIES OCCURRED FOLLOWING IV INJECTION; GPT (ALANINE TRANSAMINASE), GOT (ASPARTATE TRANSAMINASE), 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.

EXPERIMENTAL IN VITRO HEMOPERFUSION WITH ACTIVATED CHARCOAL AND AMBERLITE XAD-4 ION EXCHANGE RESIN INCREASED THE ELIMINATION OF (14)C-LABELED PHALLOIDIN FROM HEPARINIZED CATTLE BLOOD PLASMA MORE THAN HEMODIALYSIS.

THE MORTALITY RATE IN MICE DUE TO POISONING BY PHALLOIDIN WAS DECREASED BY 30-45% AFTER TREATMENT WITH SPIRONOLACTONE ALONE OR AFTER COMBINED TREATMENT WITH DIHYDROSTREPTOMYCIN, NIFUROXAZIDE, AND YEAST.

APPARENTLY DIBENZOTHIOLINE, LIKE OTHER STABILIZING COMPOUNDS, EXERTS ITS PROTECTIVE ACTION BY A NONSPECIFIC STABILIZATION OF THE CELL PLASMA MEMBRANE, PROBABLY BY RELEASE OF THIO RADICALS.

THE ADMINISTRATION OF SOMATOSTATIN IS PRESENTED AS A METHOD FOR TREATING VASCULAR HEPATIC LESIONS IN HUMANS AND OTHER MAMMALS. SOMATOSTATIN (250 MUG) INJECTED SC TO RATS 30 MINUTES BEFORE AND 30 MINUTES AFTER PHALLOIDIN (0.12 MG/100 G, IP) DECREASED HEPATIC LESIONS FROM A NONHORMONAL TREATMENT LEVEL OF 2.9 TO 0.7 (ON A SCALE OF 1-3) AND MORTALITY DECREASED FROM 100 TO 20%.

THE UPTAKE, BINDING AND ELIMINATION OF PHALLOIDIN BY LIVER WAS COMPARED IN ADULT AND BABY (17-19 DAYS OLD) RATS IN VIVO AND IN VITRO. IN BOTH GROUPS, THERE WAS NO RELATION BETWEEN THE CONCENTRATION OF THE POISON IN THE LIVER AND THE TOXICITY. ALTHOUGH BABY RATS SHOWED A SIGNIFICANTLY HIGHER TOLERANCE AGAINST PHALLOIDIN THAN THE ADULT ANIMALS, THE CONCENTRATION OF THE POISON IN THE LIVER OF BABY RATS WAS HIGHER, AND THE ELIMINATION WAS SIGNIFICANTLY SLOWER THAN IN ADULT RATS. THE VERY TIGHT BINDING AND CONCENTRATION OF PHALLOIDIN IN THE LIVER WAS EXPLAINED BY AN EXTREMELY LOW DISSOCIATION CONSTANT.

PHALLOIN AND GAMMA-AMANITIN WERE DETECTED WITHIN THE FIRST DAY AND PHALLOIDIN WITHIN THE SECOND DAY IN THE URINE OF RATS AFTER ADMINISTRATION OF AMANITA PHALLOIDES EXTRACTS.