The enterohepatic circulation of amanitin: kinetics and therapeutical implications.

Abstract

BACKGROUND:

Amatoxin poisoning induces a delayed onset of acute liver failure which might be explained by the prolonged persistence of the toxin in the enterohepatic circulation. Aim of the study was to demonstrate amanitin kinetics in the enterohepatic circulation.

METHODS:

Four pigs underwent α-amanitin intoxication receiving 0.35 mg/kg (n=2) or 0.15 mg/kg (n=2) intraportally. All pigs remained under general anesthesia throughout the observation period of 72 h. Laboratory values and amanitin concentration in systemic and portal plasma, bile and urine samples were measured.

RESULTS:

Amanitin concentrations measured 5h after intoxication of 219±5ng/mL (0.35 mg/kg) and 64±3 (0.15 mg/kg) in systemic plasma and 201±8ng/mL, 80±13ng/mL in portal plasma declined to baseline levels within 24h. Bile concentrations simultaneously recorded showed 153±28ng/mL and 99±58ng/mL and decreased slightly delayed to baseline within 32 h. No difference between portal and systemic amanitin concentration was detected after 24h.

CONCLUSIONS:

Amanitin disappeared almost completely from systemic and enterohepatic circulation within 24 h. Systemic detoxification and/or interrupting the enterohepatic circulation at a later date might be poorly effective.

• Authors: Christian Thiel, Karolin Thiel, Wilfried Klingert, Andreas Diewold, Kathrin Scheuermann, Elmar Hawerkamp, Johannes Lauber, Johannes Scheppach, Matthias H Morgalla, Alfred Königsrainer, Martin Schenk
• Journal: Toxicology letters (Toxicol Lett) Vol. 203 Issue 2 Pg. 142-6 (Jun 10 2011) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 21420474 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Alpha-Amanitin
• Amanitins
• amatoxin
• Aspartate Aminotransferases

Topics

• Alpha-Amanitin (blood, pharmacokinetics, urine)
• Amanitins (blood, pharmacokinetics, urine)
• Animals
• Aspartate Aminotransferases (blood)
• Disease Models, Animal
• Enterohepatic Circulation
• Female
• Histocytochemistry
• Liver Failure, Acute (blood, chemically induced, metabolism, urine)
• Prothrombin Time
• Swine