INHIBITION OF OXIDATION OF LOW-DENSITY-LIPOPROTEIN BY TROGLITAZONE

The effect of a new oral hypoglycemic agent troglitazone, chroman-2-yl -methoxy)benzyl]-2,4-thiazolidinedione as an antioxidant against the f ree radical-mediated oxidation of low density lipoprotein (LDL) was st udied. The oxidation of LDL gives cholesteryl ester hydroperoxide and phosphatidylcholine hydroperoxide as major primary products. Troglitaz one incorporated exogenously into LDL inhibited the oxidations of LDL induced by either aqueous or lipophilic peroxyl radicals and suppresse d the formation of lipid hydroperoxides efficiently. Ascorbic acid add ed 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 rapid ly with a galvinoxyl radical to give a chromanoxyl radical which gives the same ESR spectrum as alpha-tocopherol. This ESR spectrum disappea red rapidly when ascorbic acid was added into the system. These result s show that troglitazone acts as a potent antioxidant and protects LDL from oxidative modification.