Department of Pharmacology, Wrocław Medical University, Mikulicza-Radeckiego 2, Wrocław, Poland.
Hum Exp Toxicol. 2011 Jan;30(1):38-43. doi: 10.1177/0960327110368418. Epub 2010 Apr 8.
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.
α-鹅膏蕈碱（α-AMA）是鹅膏蕈属及其亚种（毒鹅膏和春生鹅膏）的主要毒素。α-AMA 毒性的主要机制与肝细胞中蛋白质合成受阻有关。此外，α-AMA 具有促氧化特性，这可能与其严重的肝毒性有关。本研究旨在评估 α-AMA 对人肝细胞培养物中脂质过氧化以及超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性的影响。还研究了苯唑西林（BPCN）、N-乙酰-L-半胱氨酸（ACC）和水飞蓟素（SIL）对 SOD 和 CAT 活性以及 α-AMA 致人类肝细胞培养物脂质过氧化的影响。在人肝细胞培养物中，浓度为 2μM 的 α-AMA 暴露 48 小时可导致 SOD 活性增加、CAT 活性降低以及脂质过氧化显著增加。α-AMA 引起的 SOD 和 CAT 活性变化可能通过增加过氧化氢的生成并减少该氧自由基的解毒作用来增强脂质过氧化。与没有抗氧化特性的 BPCN 相比，在含 α-AMA 的人肝细胞培养液中添加解毒剂（ACC 或 SIL）能更有效地防止脂质过氧化。
