Karolin Thiel1, Martin Schenk1, Bence Sipos2, Jan Sperveslage2, Andreas Peter3, Matthias H Morgalla4, Christian Grasshoff5, Alfred Königsrainer1, Christian Thiel6. 1. Department of General, Visceral and Transplant Surgery, University Hospital, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany. 2. Institute of General Pathology and Neuropathology, University Hospital, Liebermeisterstrasse 8, 72076, Tübingen, Germany. 3. Division of Endocrinology, Diabetology, Angiology, Nephrology, Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine, University Hospital, Ottfried-Müller-Strasse 10, 72076, Tübingen, Germany. 4. Department of Neurosurgery, University Hospital, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany. 5. Department of Anaesthesiology, University Hospital, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany. 6. Department of General, Visceral and Transplant Surgery, University Hospital, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany. christian.thiel@med.uni-tuebingen.de.
Abstract
PURPOSE: Over 90 % of fatal mushroom poisoning occurs after ingestion of amanitin-containing species. This study aimed to investigate markers indicating spontaneous liver regeneration in a porcine acute liver failure (ALF) model after α-amanitin intoxication. METHODS: German landrace pigs received either 0.15 mg/kg (n = 5) α-amanitin intravenously or 0.35 mg/kg (n = 5) intraportally. Pigs were invasively monitored and kept under general anesthesia throughout the experiment. Laboratory parameters were analyzed every 8 h. RESULTS: ALF occurred in all animals (10/10) 41 ± 3 h after intoxication. All pigs receiving 0.35 mg/kg α-amanitin and one pig receiving 0.15 mg/kg α-amanitin died 57 ± 16 h after the primary onset of ALF. Four pigs of the 0.15 mg/kg intoxication group recovered spontaneously from ALF after 56 ± 6 h. Starting at 32 h after intoxication, significantly higher values of albumin and total plasma protein could be measured in surviving animals (p < 0.05). A significant temporary increase in the tumor necrosis factor alpha (TNF-α) plasma concentration was detected 40-80 h after intoxication in recovering animals (p < 0.05). CONCLUSIONS: This porcine model represents a novel tool to analyse multiple aspects of liver regeneration following α-amanitin poisoning to allow early discrimination between a fatal course and survivors. Decreased albumin and total plasma protein concentrations in the early intoxication phase indicated a lethal outcome, while an increase in the TNF-α plasma concentration was identified as the earliest prognostic plasma marker detecting liver regeneration a long time before liver function was biochemically and clinically impaired.
PURPOSE: Over 90 % of fatal mushroom poisoning occurs after ingestion of amanitin-containing species. This study aimed to investigate markers indicating spontaneous liver regeneration in a porcine acute liver failure (ALF) model after α-amanitin intoxication. METHODS: German landrace pigs received either 0.15 mg/kg (n = 5) α-amanitin intravenously or 0.35 mg/kg (n = 5) intraportally. Pigs were invasively monitored and kept under general anesthesia throughout the experiment. Laboratory parameters were analyzed every 8 h. RESULTS:ALF occurred in all animals (10/10) 41 ± 3 h after intoxication. All pigs receiving 0.35 mg/kg α-amanitin and one pig receiving 0.15 mg/kg α-amanitin died 57 ± 16 h after the primary onset of ALF. Four pigs of the 0.15 mg/kg intoxication group recovered spontaneously from ALF after 56 ± 6 h. Starting at 32 h after intoxication, significantly higher values of albumin and total plasma protein could be measured in surviving animals (p < 0.05). A significant temporary increase in the tumor necrosis factor alpha (TNF-α) plasma concentration was detected 40-80 h after intoxication in recovering animals (p < 0.05). CONCLUSIONS: This porcine model represents a novel tool to analyse multiple aspects of liver regeneration following α-amanitinpoisoning to allow early discrimination between a fatal course and survivors. Decreased albumin and total plasma protein concentrations in the early intoxication phase indicated a lethal outcome, while an increase in the TNF-α plasma concentration was identified as the earliest prognostic plasma marker detecting liver regeneration a long time before liver function was biochemically and clinically impaired.
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: Toxicol Lett Date: 2011-03-21 Impact factor: 4.271
Authors: Christian Thiel; Karolin Thiel; Alexander Etspueler; Thomas Schenk; Matthias H Morgalla; Alfred Koenigsrainer; Martin Schenk Journal: Crit Care Date: 2010-07-22 Impact factor: 9.097