Journal
HUMAN & EXPERIMENTAL TOXICOLOGY
Volume 30, Issue 1, Pages 38-43Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0960327110368418
Keywords
alpha-amanitin; superoxide dismutase; catalase; benzylpenicillin; N-acetyl-L-cysteine; silibinin
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Funding
- Polish Ministry of Science and Higher Education [N 401 2809 33]
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alpha-Amanitin (alpha-AMA) is the main toxin of Amanita phalloides and its subspecies (A. virosa and A. verna). The primary mechanism of alpha-AMA toxicity is associated with protein synthesis blocking in hepatocytes. Additionally, alpha-AMA exhibits prooxidant properties that may contribute to its severe hepatotoxicity. The aim of the present study was to assess the effect of alpha-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 alpha-AMA were also examined. In human hepatocyte culture, 48-hour exposure to alpha-AMA at a 2-mu M 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 alpha-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 a-AMA than the addition of BPCN, possessing no antioxidant properties.
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