Abstract Presentations at the 2005 Wilderness Medical Society Meeting, Snowmass,
Colorado, July 23 to 27, 2005
Oral Presentation: Tri Tong, MD, WMS Research Grant Award Winner
Comparative Treatment of Alpha Amanitin Poisoning with N-Acetylcysteine,
Benzylpenicillin, Cimetidine, Thioctic Acid, and Silybin in a Murine Model.
Tri C. Tong, MD
1
, Mark Hernandez, MD
2
, Michael Favata, MD
2
, William H.
Richardson, MD
3
, David P. Betten, MD
1
, David A. Tanen, MD
2
1
UC San Diego Medical Center, San Diego, CA
2
Naval Medical Center San Diego, San Diego, CA
3
Palmetto Richland Memorial Hospital, Columbia, SC
Introduction: The foraging of wild mushrooms can be complicated by toxicity from
several mushroom types. Amatoxin, a peptide contained in several mushroom species,
accounts for the majority of severe mushroom poisonings by irreversibly binding to RNA
polymerase II, leading to severe hepatonecrosis. Currently, there is no antidote for severe
amatoxin poisoning.
Objective: The objective of this study was to compare the effectiveness of five potential
antidotal therapies in limiting the degree of hepatonecrosis in a randomized, controlled
murine model of amatoxin induced hepatotoxicity.
Method: 180 male ICR mice were randomized into 6 equal groups. Within each group,
21 mice were intraperitoneally (IP) injected with 0.6 mg/kg of alpha amanitin (amatoxin);
the remaining 9 were injected with 0.9% normal saline. Four hours post injection, each
group of 30 mice was randomized to one of five IP treatments (N-acetylcysteine,
benzylpenicillin, cimetidine, thioctic acid, or silybin) or normal saline. Repeat dosing was
administered IP every 4-6 hours for 48 hours. After 48 hours of treatment, each subject
was euthanized, cardiac blood was aspirated for hepatic transaminase measurements
(ALT and AST), and liver specimens were harvested to evaluate the extent of
hepatonecrosis. The degree of hepatonecrosis was determined by a pathologist blinded to
the treatment group and divided into five categories based on percent of hepatonecrosis.
Results: Amanitin significantly elevated AST in treated mice compared to controls
(Mean ± SEM, 2441 ± 615 IU/L vs. 310 ± 84, p= 0.03). No significant improvement
from control was detected in any of the antidotal therapies. Similar results were found in
regards to ALT. Histopathology demonstrated a difference between amanitin treated mice
compared to controls (rank order testing). No significant improvement in histopathology
was found with antidotal therapies.
Conclusion: In a murine model of amatoxin poisoning, treatment with N-acetylcysteine,
benzylpenicillin, cimetidine, thioctic acid, and silybin did not show efficacy in limiting
hepatonecrosis.
