title: Influence of commonly used clinical antidotes on antioxidant systems in human hepatocyte culture intoxicated with alpha-amanitin.
abstract: α-Amanitin (α-AMA) is the main toxin of Amanita phalloides and its subspecies (A. virosa and A. verna). The primary mechanism of α-AMA toxicity is associated with protein synthesis blocking in hepatocytes. Additionally, α-AMA exhibits prooxidant properties that may contribute to its severe hepatotoxicity. The aim of the present study was to assess the effect of α-AMA on lipid peroxidation and the activities of superoxide dismutase (SOD) and catalase (CAT) in human hepatocyte culture. The effects of benzylpenicillin (BPCN), N-acetyl-L-cysteine (ACC), and silibinin (SIL) on SOD and CAT activities and on lipid peroxidation in human hepatocyte culture intoxicated with α-AMA were also examined. In human hepatocyte culture, 48-hour exposure to α-AMA at a 2-μM concentration caused an increase in SOD activity, a reduction of CAT activity, and a significant increase in lipid peroxidation. Changes in SOD and CAT activity caused by α-AMA could probably enhance lipid peroxidation by increased generation of hydrogen peroxide combined with reduced detoxification of that oxygen radical. The addition of antidotes (ACC or SIL) to the culture medium provided more effective protection against lipid peroxidation in human hepatocytes intoxicated with α-AMA than the addition of BPCN, possessing no antioxidant properties.
authors.affiliation: Department of Pharmacology, Wrocław Medical University, Mikulicza-Radeckiego 2, Wrocław, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Magdalan
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Piotrowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gomułkiewicz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sozański
authors.forename: Adam
authors.initials: A
authors.lastname: Szeląg
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziegięl
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D053959:Alpha-Amanitin / Q000633:toxicity*; D000545:Amanita / Q000737:chemistry; D000931:Antidotes / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009145:Mushroom Poisoning / Q000188:drug therapy; D019384:Nucleic Acid Synthesis Inhibitors / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D010400:Penicillin G / Q000494:pharmacology; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D053959:Alpha-Amanitin; D000931:Antidotes; D000975:Antioxidants; D019384:Nucleic Acid Synthesis Inhibitors; D016877:Oxidants; D012838:Silymarin; D000077385:Silybin; D002374:Catalase; D013482:Superoxide Dismutase; D010400:Penicillin G; D000111:Acetylcysteine