PRINCIPLES OF TOXICOLOGY

418 PROPERTIES AND EFFECTS OF NATURAL TOXINS AND VENOMS
Figure 17.3 The death cap mushroom, Amanita phalloides. This is the most poisonous mushroom in the world,
and occurs in Asia, Europe, and North America. Mushrooms belonging to this genus account for >95 percent of
reported human fatalities to mushrooms.
about 20 times more toxic than the phallotoxins, so they are the toxins that must be reckoned with the
most. They are particularly hepatotoxic because of their ability to be taken up through the bile acid
transport mechanism. Once they enter the hepatic parenchymal cell, they inhibit the key transcriptional
enzyme RNA polymerase within the nucleus, thus shutting down the ability of the cell to replace
cellular proteins, which are continually being broken down. This results in hepatic necrosis and death
in 10–30 percent of intoxicated persons. A major problem in diagnosing and treating amanita poisoning
is that the characteristic symptoms due to amatoxin appear only about 15 h after ingestion, regardless
of the dose. This represents the minimum time for uptake and enzyme inhibition by the toxin, and for
the hepatic protein depletion to begin affecting hepatic function. About 6–10 h after ingestion one
experiences gastric distress and diarrhea caused by the phallotoxins. They bind to the actin filaments
in the inner surface of the cell membrane, preventing them from dissociating into monomeric actin,
which is required for normal cell functioning.
Amatoxins can be detected in the blood and urine with various techniques, in order to verify the
cause of the poisoning. Ingestion of oral activated charcoal is effective in absorbing much of the toxins
if it is done within 4 hours after ingestion. Of course, the victim may not yet have experienced many
symptoms at that critical time.
Other species of mushrooms produce alkaloidal toxins, which are much less life-threatening.
Muscarine, isolated over a century ago and used in classifying cholinergic receptors, is one example.
Its actions are quite predictable as well as swift. Fortunately, specific antidotes such as the muscarinic
antagonist atropine exist. Other mushrooms produce biogenic amines such as bufotenin (originally
isolated from venom glands of the toad Bufo) and psilocybin. These are hallucinogenic compounds