Inhibition of oxidation of low density lipoprotein by troglitazone.
The effect of a new oral hypoglycemic agent troglitazone, (+/-)-5-[4-(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)benz yl]-2,4-thiazolidinedione as an antioxidant against the free radical-mediated oxidation of low density lipoprotein (LDL) was studied. The oxidation of LDL gives cholesteryl ester hydroperoxide and phosphatidylcholine hydroperoxide as major primary products. Troglitazone incorporated exogenously into LDL inhibited the oxidations of LDL induced by either aqueous or lipophilic peroxyl radicals and suppressed the formation of lipid hydroperoxides efficiently. Ascorbic acid added into the aqueous phase spared both endogenous alpha-tocopherol and troglitazone in LDL. It was also found by absorption spectroscopic and electron spin resonance (ESR) studies that troglitazone reacted rapidly with a galvinoxyl radical to give a chromanoxyl radical which gives the same ESR spectrum as alpha-tocopherol. This ESR spectrum disappeared rapidly when ascorbic acid was added into the system. These results show that troglitazone acts as a potent antioxidant and protects LDL from oxidative modification.
Noguchi
N
N
Research Center for Advanced Science and Technology, University of Tokyo, Japan
Sakai
H
H
Kato
Y
Y
Tsuchiya
J
J
Yamamoto
Y
Y
Niki
E
E
Horikoshi
H
H
Kodama
T
T
D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000737:chemistry*; D010084:Oxidation-Reduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D000077288:Troglitazone; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001559:Benzhydryl Compounds; D002839:Chromans; D005609:Free Radicals; D007004:Hypoglycemic Agents; D008077:Lipoproteins, LDL; D013844:Thiazoles; D045162:Thiazolidinediones; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D000077288:Troglitazone; D001205:Ascorbic Acid; C020338:galvinoxyl