amatoxin and Liver-Failure

Mushroom toxicity is the main branch of foodborne poisoning, and liver damage caused by amatoxin poisoning accounts for more than 90 % of deaths due to mushroom poisoning. Alpha-amatoxin (α-AMA) has been considered the primary toxin from amatoxin-containing mushrooms, which is responsible for hepatotoxicity and death. However, the mechanism underlying liver failure due to α-AMA remains unclear. This study constructed animal and cell models. In the animal experiments, we investigated liver injury in BALB/c mice at different time points after α-AMA treatment, and explored the process of inflammatory infiltration using immunohistochemistry and western blotting. Then, a metabonomics method based on gas chromatography mass spectrometry (GCMS) was established to study the effect of α-AMA on liver metabonomics. The results showed a significant difference in liver metabolism between the exposed and control mice groups that coincided with pathological and biochemical indicators. Moreover, 20 metabolites and 4 metabolic pathways related to its mechanism of action were identified, which suggested that energy disorders related to mitochondrial dysfunction may be one of the causes of death. The significant changes of trehalose and the fluctuation of LC3-II and sqstm1 p62 protein levels indicated that autophagy was also involved in the damage process, suggesting that autophagy may participate in the clearance process of damaged mitochondria after poisoning. Then, we constructed an α-AMA-induced human normal liver cells (L-02 cells) injury model. The above hypothesis was further verified by detecting cell necrosis, mitochondrial reactive oxygen species (mtROS), mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (Δψ m), and cellular ATP level. Collectively, our results serve as direct evidence of elevated in vivo hepatic mitochondrial metabolism in α-AMA-exposed mice and suggest that mitochondrial dysfunction plays an important role in the early stage of α-AMA induced liver failure.

Topics: Amanitins; Animals; Cell Line; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Energy Metabolism; Humans; Liver; Liver Failure; Metabolomics; Mice, Inbred BALB C; Mitochondria, Liver; Mushroom Poisoning; Time Factors

Indication of liver transplantation in acute liver failure following amatoxin intoxication is still uncertain.. One hundred and ninety-eight patients were studied retrospectively. The laboratory parameters alanine-aminotransferase, serum bilirubin, serum creatinine and prothrombin index were analyzed over time. Predictors of fatal outcome and survival were determined by receiver-operating-characteristic and sensitivity-specificity analysis.. Twenty-three patients died in the median 6.1 days (range, 2.7-13.9 days) after ingestion. Using a single parameter as predictor of fatal outcome the area under the receiver-operating-characteristic curve of prothrombin index (0.96) and serum creatinine (0.93) were both significantly greater (P<0.05) compared with serum bilirubin (0.82) and alanine-aminotransferase (0.69). Prediction of fatal outcome had an optimum, if a prothrombin index less than 25% was combined with a serum creatinine greater than 106 micromol/l from day 3 after ingestion onwards (sensitivity 100%, 95% confidence interval 87-100; specificity 98%, 95% confidence interval 94-100). The median time period between the first occurrence of this predictor in non-survivors and death was 63h (range, 3-230h).. A decision model of liver transplantation following amatoxin intoxication using prothrombin index in combination with serum creatinine from day 3 to 10 after ingestion enables an early and reliable assessment of outcome.

Topics: Adolescent; Adult; Alanine Transaminase; Amanitins; Bilirubin; Child; Humans; Liver Failure; Liver Transplantation; Mushroom Poisoning; Predictive Value of Tests; Prothrombin Time; Retrospective Studies; Survival Analysis

Experiences of liver transplantation after Amanita phalloides poisoning were analysed in anaesthetic and intensive therapist point of view based on 3 cases. Cardiac problems were found at all patients during the postoperative period. Probably the amatoxin has cardiotoxic effect or a part of phallotoxins are absorbed despite cooking and caused reversible cardiac function impairment. Pancreatitis, DIC, gastrointestinal bleeding, acute renal failure were found at all patients, therefore liver transplantation is only a part of the treatment, complex therapy is necessary in this cases.

Topics: Acute Kidney Injury; Adult; Amanita; Amanitins; Anesthesia, General; Child; Combined Modality Therapy; Critical Care; Disseminated Intravascular Coagulation; Electrocardiography; Gastrointestinal Hemorrhage; Heart Conduction System; Humans; Liver Failure; Liver Transplantation; Male; Mushroom Poisoning; Pancreatitis

The purpose of this study was to develop a clinically relevant porcine model of fulminant hepatic failure (FHF) by means of administration of amatoxin and endotoxin.. Pigs were intraportally administered only saline in group 1 (n = 3), 1 microg/kg of lipopolysaccharide (LPS) in group 2 (n = 4), 0.1 mg/kg of alpha-amanitin in group 3 (n = 5), and amanitin plus LPS in group 4 (n = 9).. All the pigs in groups 1 and 2 survived with minimal changes in liver function tests. In contrast to the 60% mortality in group 3, all the pigs in group 4 died within 96 h, with a significant increase in aspartate transaminase at 24 h (9,757 +/- 2,167 IU/I). In addition, they demonstrated severe metabolic disorders, such as serum lactate accumulation, hypoglycemia, coagulopathy, plasma amino acid imbalance, and hyperammonemia. The intracranial pressure significantly increased to 17.8 +/- 2.5 mmHg immediately before death. Reversal of FHF in these pigs following orthotopic liver transplantation confirmed that the toxicity is liver-specific and that the graft liver is unaffected.. This porcine model of FHF induced by a combination of amanitin and LPS will be of much use in the development of new therapies for human FHF.

Topics: Amanitins; Animals; Disease Models, Animal; Humans; Intracranial Hypertension; Lipopolysaccharides; Liver; Liver Failure; Liver Transplantation; Male; Swine

Four cases of severe Lepiota poisoning, including three which developed toxic fulminant hepatitis treated by orthotopic hepatic transplantation, are reported here. The toxicity of the Lepiota is discussed as well as the indications for hepatic transplantation in poisonings due to amatoxin-containing mushrooms.

Topics: Adult; Amanitins; Child; Electroencephalography; Female; Humans; Liver Failure; Liver Transplantation; Male; Mushroom Poisoning