amanitins and Liver-Diseases

Silibinin is the most active component of a complex of flavonoids -silymarin contained in fruit milk thistle (Sylibum marianum). Its mechanism of action is complex and highly beneficial in protecting hepatocytes. On the one hand this compound blocks the penetration of various toxins (for example amanitin) into the hepatocytes not allowing in this way for the cell death and on the other hand, it prevents apoptosis through intracellular. It protects the liver from oxidative intracellular free radicals by increasing the activity of enzyme superoxide dismutase and peroxidase, as well as by increasing the concentration of glutathione and the activity of the peroxidase. Silibinin strengthens and stabilizes the cell membranes, inhibits the synthesis of prostaglandins associated with the lipid peroxidation and promotes regeneration of liver through the stimulation of protein synthesis and effect on the production of new hepatocytes. A particularly interesting topic from the perspective of a toxicologist is the application of silibinin in Amanita phalloides poisoning. Clinical trials conducted in this respect are very encouraging. The other beneficial application of silibinin is in therapy of the alcoholic liver cirrhosis. The evidence shows that the use of silymarin leads to a significant reduction in liver-related mortality and even reduction in the number of patients with encephalopathy in the course of the disease. Application of silibinin goes beyond liver disease and expands in the direction of cancer and even diabetes. What is interesting is the fact, that the substance of herbal origin occurring in the environment is so strong, favorable, beneficial and multidirectional. Science has contributed to improving the bioavailability of silibinin thus making it more effective.

Topics: Amanita; Amanitins; Chemical and Drug Induced Liver Injury; Hepatocytes; Humans; Lipid Peroxidation; Liver Diseases; Liver Regeneration; Mushroom Poisoning; Peroxidases; Prostaglandins; Protective Agents; Silybin; Silymarin; Superoxide Dismutase

In this study, the toxicology of A. exitialis, a lethal mushroom found in China, and the toxicokinetics of peptide toxins contained in it were evaluated. Beagles were fed A. exitialis powder (20 or 60 mg/kg) in starch capsules, after which they were assessed for signs of toxicity, as well as biochemical and pathological changes. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to assay the peptide toxins. The total peptide toxins in A. exitialis was 3482.6 ± 124.94 mg/kg. The beagles showed signs of toxicity, such as vomiting and diarrhea, at 12-48 h following ingestion of A. exitialis. Furthermore, alanine transaminase and aspartate transaminase levels in plasma, as well as prothrombin time and activated partial thromboplastin time peaked at 36 h post A. exitialis ingestion. Furthermore, total bilirubin and alkaline phosphatase levels peaked at 48 h after A. exitialis ingestion. Three dogs that were administered 60 mg/kg A. exitialis died at 24-72 h after ingesting the capsules. Additionally, liver histopathological examinations showed hemorrhagic necrosis of hepatocytes. α-Amanitin, β-amanitin, and phallacidin were rapidly absorbed and eliminated from plasma after A. exitialis was ingested. A long latency period (12-24 h post A. exitialis ingestion) was observed in the dogs before the onset of gastrointestinal symptoms. There was acute liver damage thereafter. Gastric lavage and enhanced plasma clearance methods such as hemodialysis, hemoperfusion, or plasma exchange may be ineffective in removing amatoxins from blood at 12 h post A. exitialis ingestion. Enhanced excretion of amatoxins in urine could be effective within 2 days after ingestion of A. exitialis because amatoxins in 0-2 d urine accounted for more than 90% of the total urine excretion.

Topics: Alanine Transaminase; Amanita; Amanitins; Animals; Aspartate Aminotransferases; Dogs; Fungal Proteins; Liver Diseases; Male; Mushroom Poisoning; Partial Thromboplastin Time; Peptides, Cyclic; Prothrombin Time; Toxicokinetics

Poisoning with amanitin-containing hepatotoxic mushrooms demands extensive efforts from clinicians, toxicologists, and pathologists. Presumptive diagnoses are established by positive identification of the suspect mushroom along with the occurrence of consistent clinical signs. If the animal dies, hepatic lesions may suggest exposure to amanitin-containing mushrooms; however, lesions are nonspecific. A 15-week-old female Dachshund was presented to the referring veterinarian for acute onset of lethargy that quickly progressed to sternal recumbency. Despite supportive care, the dog remained lethargic and died approximately 12 hours after initial presentation. A pale tan liver was noted at necropsy. Microscopically, the liver showed panlobular coagulative necrosis of hepatocytes. A presumptive diagnosis of amanitin poisoning was based on suspect history of exposure to mushrooms, clinical signs, and pathologic findings. Exposure to amanitin was confirmed through detection of alpha-amanitin in the liver by liquid chromatography/mass spectrometry. The objective of this case report is to illustrate the essential components to a successful diagnostic work-up of a suspect case of hepatotoxic mushroom poisoning. Although hepatotoxic mushroom poisoning has been documented in dogs before, confirmatory techniques for biologic specimens have not been used previously in diagnostic investigations.

Topics: Amanita; Amanitins; Animals; Chromatography, Liquid; Dog Diseases; Dogs; Fatal Outcome; Female; Immunohistochemistry; Liver Diseases; Mass Spectrometry; Mushroom Poisoning

Topics: Adolescent; Adult; Amanita; Amanitins; Child; Child, Preschool; Female; Hemoperfusion; Humans; Liver Diseases; Liver, Artificial; Male; Mushroom Poisoning; Plasma Exchange; Sorption Detoxification

Acute phase responses to intragastric administration of a single dose of CCl(4) were examined with albumin mRNA turnover as a marker. Based on the combination of the changes in stability of albumin mRNA and activity of transcription of its gene, the entire course of liver injury was classified into three stages, the first stage for aggravation of injury until 9 h, the second from 9 to 24 h, and the third for repair of injury or regeneration of liver after 48 h. Liver S100 fractions from normal and CCl(4)-treated rats contained, in total, 11 polypeptides cross-linked with part of albumin mRNA, although they did not appear to be specific to this mRNA. Their profiles were altered together with the changes in stability of albumin mRNA in different stages. These findings suggest that the polypeptides with distinct properties play roles in physiologically significant processes involved in utilization and turnover of albumin mRNA, apparently altering its stability.

Topics: Acute-Phase Reaction; Albumins; Amanitins; Animals; Base Sequence; Binding, Competitive; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Gene Expression Regulation; Half-Life; Liver; Liver Diseases; Male; Molecular Weight; Peptides; Protein Binding; Rats; Rats, Wistar; RNA Probes; RNA Stability; RNA-Binding Proteins; RNA, Messenger; Substrate Specificity; Time Factors; Transcription, Genetic

Topics: Amanitins; Animals; Chemical and Drug Induced Liver Injury; Flavonoids; Injections, Intraperitoneal; Liver Diseases; Male; Mice; Silymarin

Topics: Aflatoxins; Amanitins; Chemical and Drug Induced Liver Injury; Humans; Hydrocarbons, Halogenated; Liver Cirrhosis, Alcoholic; Liver Diseases; Liver Diseases, Alcoholic; Porphyrins