Tomita M, Okuyama T
Department of Legal Medicine, Kawasaki Medical School, Kurashiki, Japan.
Arch Toxicol. 1994;68(3):187-92. doi: 10.1007/s002040050053.
Toxicosis due to paraquat, a redox cycling xenobiotic, is still a subject of much debate. In the present study on lipid peroxidation, paraquat had a biphasic effect on the malondialdehyde (MDA) level in rat liver microsomes; stimulation at the initial stage (within 10 min) and depression at the later stage. Although paraquat increased the initial rate of NADPH oxidation dose-dependently, the rate was not necessarily parallel with the increase in the MDA level. The MDA level increased linearly up to 0.1 mM paraquat added, but then it attained a plateau. The stimulation obtained by paraquat within 10 min was absolutely dependent on exogenous Fe2+ ion and NADPH, and the stimulation was entirely SOD sensitive, while the iron-driven increase in MDA was 20% sensitive. Thus, there were different mechanisms between iron-driven lipid peroxidation and paraquat-modified peroxidation. Catalase increased the level, but mannitol, a scavenger of OH, had no effect. EPR spectra showed that superoxide was formed dose-dependently up to 0.1 mM paraquat and that it attained a plateau at the same as MDA level described above. From these results, we concluded that paraquat stimulates lipid peroxidation through a mechanism dependent on the superoxide complex involving Fe2+ ion.
百草枯作为一种可进行氧化还原循环的外源性物质，其引起的中毒现象仍是一个备受争议的话题。在当前关于脂质过氧化的研究中，百草枯对大鼠肝脏微粒体中的丙二醛（MDA）水平具有双相作用：在初始阶段（10分钟内）起刺激作用，而在后期起抑制作用。尽管百草枯剂量依赖性地增加了NADPH氧化的初始速率，但该速率并不一定与MDA水平的增加平行。在添加的百草枯浓度达到0.1 mM之前，MDA水平呈线性增加，但随后达到平台期。百草枯在10分钟内产生的刺激作用绝对依赖于外源性Fe2+离子和NADPH，且该刺激作用完全对超氧化物歧化酶（SOD）敏感，而铁驱动的MDA增加仅有20%敏感。因此，铁驱动的脂质过氧化和百草枯介导的过氧化之间存在不同的机制。过氧化氢酶会增加MDA水平，但OH清除剂甘露醇则没有作用。电子顺磁共振（EPR）光谱显示，在百草枯浓度达到0.1 mM之前，超氧化物呈剂量依赖性形成，且在与上述MDA水平相同的时候达到平台期。从这些结果来看，我们得出结论：百草枯通过一种依赖于涉及Fe2+离子的超氧化物复合物的机制来刺激脂质过氧化。
