Higuchi Akihiro, Yonemitsu Kosei, Koreeda Ako, Tsunenari Shigeyuki
Department of Forensic Medicine, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan.
Toxicology. 2003 Feb 1;183(1-3):143-9. doi: 10.1016/s0300-483x(02)00512-7.
Recently we have reported that epigallocatechin gallate (EGCg), a major component of Japanese green tea, significantly increased the survival rate of paraquat (Pq) poisoned mice. This paper describes two biochemical activities of EGCg, which relate to its protective effects against Pq toxicity. EGCg inhibited Pq-induced microsomal malondialdehyde (MDA) productions in rat liver microsome system containing 40 microM FeSO(4). Forty micromolar EGCg inhibited MDA production significantly. EGCg may inhibit the Pq-induced MDA production by at least two mechanisms. One may be iron-chelating activity as the inhibition disappeared when excess amounts of FeSO(4) were added to the reaction mixture, which indicated that EGCg reduced iron driven lipid peroxidation by pulling out available irons in the reaction mixture. The other is radical scavenging activity. EGCg scavenged DMPO-OOH spin adducts generated by the microsome-Pq system. The dose response curve of EGCg was similar to that obtained by ascorbic acid which is a typical water-soluble radical scavenger. Although ascorbic acid had a potential activity of scavenging superoxide radicals, it can not be recommended to use for the treatment of Pq poisoning, because ascorbic acid acts as a pro-oxidant in the presence of free transition metal ions by accelerating the Fenton reaction (Fe(2+)+H(2)O(2)-->Fe(3+)+OH(-)+OH*), which is responsible for lipid peroxidation. On the contrary, EGCg inhibited iron-driven lipid peroxidation presumably not only by chelating to Fe ions but also by scavenging superoxide radicals, which are responsible for the reduction of ferric (Fe(3+)) to ferrous (Fe(2+)) that catalyzes the Fenton reaction. Chelating and radical scavenging activity of EGCg can be expected simultaneously in the occurrence of Pq toxicity, which may explain the protective effects of EGCg against Pq toxicity.
最近我们报道了表没食子儿茶素没食子酸酯（EGCg），一种日本绿茶的主要成分，能显著提高百草枯（Pq）中毒小鼠的存活率。本文描述了EGCg的两种生化活性，这与其对Pq毒性的保护作用相关。在含有40微摩尔硫酸亚铁（FeSO₄）的大鼠肝微粒体系统中，EGCg抑制了Pq诱导的微粒体丙二醛（MDA）生成。40微摩尔的EGCg显著抑制了MDA的生成。EGCg可能通过至少两种机制抑制Pq诱导的MDA生成。一种可能是铁螯合活性，因为当向反应混合物中加入过量的FeSO₄时，这种抑制作用消失了，这表明EGCg通过去除反应混合物中可用的铁来减少铁驱动的脂质过氧化。另一种是自由基清除活性。EGCg清除了微粒体 - Pq系统产生的DMPO - OOH自旋加合物。EGCg的剂量反应曲线与典型的水溶性自由基清除剂抗坏血酸所获得的曲线相似。尽管抗坏血酸具有清除超氧自由基的潜在活性，但它不能被推荐用于治疗Pq中毒，因为抗坏血酸在游离过渡金属离子存在下通过加速芬顿反应（Fe²⁺ + H₂O₂ → Fe³⁺ + OH⁻ + OH*）作为促氧化剂，而芬顿反应会导致脂质过氧化。相反，EGCg可能不仅通过与铁离子螯合，还通过清除超氧自由基来抑制铁驱动的脂质过氧化，超氧自由基负责将催化芬顿反应的三价铁（Fe³⁺）还原为二价铁（Fe²⁺）。在Pq毒性发生时，可以同时预期EGCg的螯合和自由基清除活性，这可能解释了EGCg对Pq毒性的保护作用。
