Inhibitory activity of epigallocatechin gallate (EGCg) in paraquat-induced microsomal lipid peroxidation--a mechanism of protective effects of EGCg against paraquat toxicity.
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.
Higuchi
Akihiro
A
Department of Forensic Medicine, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan. yonemie@kumamoto-u.ac.jp
Yonemitsu
Kosei
K
Koreeda
Ako
A
Tsunenari
Shigeyuki
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000737:chemistry; D003676:Deferoxamine / Q000378:metabolism; D004347:Drug Interactions; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D006540:Herbicides / Q000378:metabolism* / Q000633:toxicity*; D007502:Iron Chelating Agents / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D019097:Spin Trapping; D013481:Superoxides / Q000378:metabolism; D013662:Tea
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D006540:Herbicides; D007502:Iron Chelating Agents; D008054:Lipid Peroxides; D013662:Tea; D013481:Superoxides; D008315:Malondialdehyde; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D002392:Catechin; C045651:epigallocatechin gallate; D003676:Deferoxamine; D010269:Paraquat