Watanabe N, Shiki Y, Morisaki N, Saito Y, Yoshida S
Biochim Biophys Acta. 1986 Oct 1;883(3):420-5. doi: 10.1016/0304-4165(86)90279-5.
Paraquat causes failure of multiple organs including the liver in humans. The kinetics and mechanism of paraquat intoxication were studied using cultured rat hepatocytes. Paraquat induced time- and dose-dependent lactate dehydrogenase release, lipid peroxidation, and cell death, estimated as decrease in protein in cells attached to culture dishes. However, the increase in lipid peroxidation occurred after lactate dehydrogenase release had reached a plateau. Vitamin E inhibited the inductions of all these cytotoxic effects of paraquat. Kinetic studies showed that lipid peroxidation was a better indicator of cell death than lactate dehydrogenase release, because vitamin E inhibited the induction of cell death even when added 6 h after paraquat, when lactate dehydrogenase release had reached a plateau but lipid peroxidation had not. The present results strongly suggest that paraquat exerts its cytotoxicity by a mechanism involving oxidation reactions.
百草枯可导致人体包括肝脏在内的多个器官功能衰竭。利用培养的大鼠肝细胞研究了百草枯中毒的动力学和机制。百草枯可诱导时间和剂量依赖性的乳酸脱氢酶释放、脂质过氧化以及细胞死亡，细胞死亡以附着于培养皿的细胞中蛋白质含量的减少来估算。然而，脂质过氧化的增加发生在乳酸脱氢酶释放达到平台期之后。维生素E可抑制百草枯所有这些细胞毒性作用的诱导。动力学研究表明，脂质过氧化比乳酸脱氢酶释放更能作为细胞死亡的指标，因为即使在百草枯作用6小时后添加维生素E（此时乳酸脱氢酶释放已达到平台期，但脂质过氧化尚未发生），它仍能抑制细胞死亡的诱导。目前的结果强烈表明，百草枯通过涉及氧化反应的机制发挥其细胞毒性作用。
