Page 1025 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Mushroom Toxins Chapter | 67 957

VetBooks.ir Wieland, 1983). The decrease in mRNA and associated and treatment may be necessary. Clinical signs of hypo-
glycemia in dogs and cats include seizures, coma, and
decrease in protein synthesis result in hepatocyte necrosis.
death. Finally, it is important to note that not all cases
Cells with a high metabolic rate, such as hepatocytes,
crypt cells, and proximal convoluted tubules of the kid- present with the classic four stages. In cases of large
neys, are most commonly affected. Although this mecha- exposure to amanitins, or ingestion by puppies, the animal
nism is well established, research has confirmed may die within 24 h (Cole, 1993).
additional cellular effects that contribute to pathogenesis.
In mice and cultured dog hepatocytes, apoptosis contrib- TOXICITY
uted to amanitin-induced liver failure (Leist et al., 1997;
Magdalan et al., 2010b), and in pancreatic rat islets Amanitins are extremely toxic, and poisonings have been
α-amanitin resulted in a dose-dependent insulin-releasing confirmed in dogs, horses (Beug, 2009), and cattle (Yee
and a β-cytotoxic effect (De Carlo et al., 2003). Acute et al., 2012). The i.v. LD 50 of α-amanitin in dogs is
tubular necrosis in the kidneys is believed to be a result 0.1 mg/kg body weight (Faulstich et al., 1985). Based on
of reabsorption of amanitins by renal tubules after an oral dosing study in dogs, the oral LD 50 for methyl-
glomerular filtration. γ-amanitin was estimated to be 0.5 mg/kg body weight. In
The clinical course is divided into four phases, with mice and rats, the i.v. LD 50 of α-amanitin is 0.35 and 3 or
the initial phase being the latency period of approximately 4 mg/kg body weight, respectively, illustrating significant
6 12 h. The second phase is characterized by severe gas- species differences. Guinea pigs and rabbits are consid-
trointestinal signs, such as nausea, vomiting, bloody diar- ered to be approximately equally sensitive as dogs to
rhea, and severe abdominal pain. In dogs, the onset of amanitins, with i.v. LD 50 sof α-amanitin of 0.1 and
clinical signs is generally 6 24 h after mushroom inges- 0.2 mg/kg, respectively. In humans, the estimated oral
tion. Beagles experimentally given an oral sublethal dose LD 50 of α-amanitin is 0.1 mg/kg body weight.
of amanitins developed vomiting and diarrhea at 16 h. Considering the average concentration of amanitins per
Gastrointestinal signs improved after 60 h (Vogel et al., mushroom, one A. phalloides has the potential to kill a
1984). The gastroenteric phase is often followed by a lag dog or horse.
period of several hours to a few days during which the
human or animal will appear to have recovered. During
TREATMENT
this third phase, close monitoring of liver and kidney
function is essential in order to prevent misdiagnosis. The No specific antidote for amanitins exists, and thus there is
final stage begins approximately 36 84 h after exposure wide variability in treatment and overall response rate.
to amanitins. In this stage, fulminant hepatic failure with Prompt measures, including decontamination and support-
subsequent coagulation disorders, encephalopathy, and ive care, are required to improve prognosis. Even with
renal failure may occur. In dogs, significant elevations in supportive measures, the reported mortality rate from
serum of aspartate aminotransferase (AST), alanine ami- Amanita poisoning in humans is 15% 20%, and it is
notransferase (ALT), alkaline phosphatase, and bilirubin often higher in children (Enjalbert et al., 2002). In
are commonly observed (Vogel et al., 1984; Kallet et al., humans with amanitin poisoning, silibinin, penicillin, and
1988). In humans, a combination of the prothrombin (PT) N-acetylcysteine (NAC) are most commonly recom-
index along with serum creatinine concentrations deter- mended, although clinical efficacy data are ambiguous.
mined between three and 10 days after ingestion was Similar treatment approaches have been used with variable
most useful as a predictor of death (Ganzert et al., 2005). success rates in dogs suffering from amanitin poisoning
Although no controlled study exists in dogs, PT and par- (Tegzes and Puschner, 2002).
tial thromboplastin may provide critical information for Silibinin and penicillin reduce the uptake of amanitins
case assessment (Tegzes and Puschner, 2002). In pigs, into hepatocytes. Silibinin (also known as silybin) is the
decreased albumin and total plasma protein concentrations main component of silymarin, which is extracted from the
in the first 24 to 24 h indicated a lethal outcome (Thiel common milk thistle (Silybum marianum). Silibinin is
et al., 2014). Clinical signs of renal failure include poly- also a free radical scavenger, and it has immunostimula-
uria, polydypsia, vomiting, and anorexia. Severe hypogly- tory and iron binding properties (Mayer et al., 2005). In
cemia can occur in dogs after the gastrointestinal phase, Europe, a silibinin-contained product (Legalon-Sil) is a
and it is associated with the breakdown of liver glycogen well-established and approved treatment for amanitin poi-
(Puschner et al., 2007). In a study in which dogs were sonings in humans. Treatment consists of a 5 mg/kg load-
given lethal doses of amanitin toxins or pieces of A. phal- ing dose i.v. followed by 20 mg/kg/day via continuous
loides, 50% of dogs died from hypoglycemia 1 or 2 days infusion (Karlson-Stiber and Persson, 2003) until coagulo-
after exposure (Faulstich and Fauser, 1980). In clinical pathy is no longer present and liver function tests have
cases, dogs must be monitored closely for hypoglycemia, returned significantly toward normal. In 2009, an open