Activation of rat liver microsomal glutathione S-transferase by gallic acid.
The effect of phenolic antioxidants on the rat liver microsomal glutathione S-transferase (MGST1) was investigated in vitro. When microsomes were incubated with various polyphenolic antioxidants, gallic acid (3,4,5-trihydroxybenzoic acid) markedly increased MGST1 activity and the increase was prevented in the presence of superoxide dismutase (SOD) or catalase. The MGST1 activity increased by gallic acid was decreased by further incubation with sodium arsenite, a sulfenic acid reducing agent, but was not with dithiothreitol, a disulfide bond reducing agent. The incubation of microsomes with gallic acid in the presence of the NADPH generating system which generates reactive oxygen species (ROS) through cytochrome P-450 system increased the MGST1activity in spite of scavenging the ROS and the increase was also depressed by SOD/catalase. The increase of MGST1 activity by gallic acid was prevented by co-incubation with a stable radical, 1,1-diphenyl-2-picrylhydrazyl or ferric chloride. These results suggest that the gallic acid acts as a pro-oxidant and activates MGST1 through oxidative modification of the enzyme.
Shinno
Etsuki
E
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.
Shimoji
Miyuki
M
Imaizumi
Naoki
N
Kinoshita
Shizuka
S
Sunakawa
Hajime
H
Aniya
Yoko
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020536:Enzyme Activators / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000737:chemistry; D005707:Gallic Acid / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008163:Luminescent Measurements; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology
D000975:Antioxidants; D020536:Enzyme Activators; D016166:Free Radical Scavengers; D005609:Free Radicals; D005707:Gallic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase