Ferrous ion supported in vivo lipid peroxidation induced by paracetamol--its relation to hepatotoxicity.
Ferrous ion supported in vivo lipid peroxidation induced by paracetamol--its relation to hepatotoxicity.
复制标题
亚铁离子支持对乙酰氨基酚诱导的体内脂质过氧化——其与肝毒性的关系。
DOI：
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发表时间：
1986
期刊：
影响因子：
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通讯作者：
C. Siegers
中科院分区：
文献类型：
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作者：
M. Younes;S. Cornelius;C. Siegers
用400 mg/kg的扑热息痛或20 mg/kg的Fe2+处理小鼠，没有引起体内的脂质过氧化，这一点从乙烷的呼出率中得到了证明。然而，两者的联合治疗导致了脂质过氧化的九倍以上的增强。在谷胱甘肽耗竭的小鼠中，与各自的对照组相比，单独使用这两种药物的小鼠的乙烷呼出量几乎翻了一番。在这里，同样，两者的治疗导致体内脂质过氧化反应甚至增加了26倍。这些结果表明，扑热息痛的氧化还原代谢产物需要铁离子来启动脂质过氧化。在两组同时使用Fe2+和扑热息痛治疗的小鼠以及仅使用扑热息痛治疗的谷胱甘肽耗竭小鼠中都发现了显著的肝脏毒性，尽管脂质过氧化的速度不同，但这三组小鼠的肝脏损伤程度是相同的。这种肝毒性反应与乙烷呼气的分离表明，至少脂质过氧化不是扑热息痛对肝细胞产生毒性的唯一机制。
Treatment of mice with 400 mg/kg paracetamol or 20 mg/kg Fe2+ did not evoke in vivo lipid peroxidation as evidenced by the rate of ethane exhalation. The combined treatment with both, however, led to a more than ninefold enhancement of lipid peroxidation. In glutathione-depleted mice treatment by either agent alone almost doubled the rate of ethane exhalation as compared to the respective control group. Here, again, treatment with both led to an even 26-fold increase in in vivo-lipid peroxidation. These results indicate that iron ions are needed to initiate lipid peroxidation by a redox-cycling metabolite of paracetamol. Marked hepatotoxicity was seen in both groups of mice treated with both Fe2+ and paracetamol as well as in glutathione-depleted mice treated with paracetamol only, the degree of liver damage being identical in all three groups despite of the different rates of lipid peroxidation. This dissociation of hepatotoxic response from ethane exhalation indicates that lipid peroxidation is at least not the sole mechanism by which paracetamol exerts its toxicity towards liver cells.