AAPH-induced Oxidation Research Articles

Inhibitory Effects of Catechol Derivatives on Oxidation of Soybean Phosphatidylcholine Liposomes Induced by Hydrophilic and Hydrophobic Free Radical Initiators.

Effects of pyrocatechol and six of its monosubstituents on oxidation of soybean phosphatidylcholine liposome induced by hydophilic free radical initiator, 2, 2'-azobis(2-amidinopropane)dihydrochloride (AAPH), and hydrophobic free radical initiator, 2, 2'-azobis(2, 4-dimethylvaleronitrile) (AMVN), were determined and relationships with their redox potentials and hydrophobic parameters were studied for their inhibitory effects by regression analysis. Inhibitory potencies of the catechol compounds on hydrophilic AAPH-induced oxidation clearly correlated with their redox potentials, whereas no significant effects of the hydrophobicities of the compounds were found. These results indicated that scavenging activities of these compounds on AAPH-initiated radical chain reactions were controlled by their electron donor activities. Inhibitory potencies of these compounds on hydrophobic AMVN-induced oxidation of liposome, in contrast, were significantly correlated with their hydrophobicity, although regression analysis revealed that their electron donor activities were also important.

Effects of ebselen and probucol on oxidative modifications of lipid and protein of low density lipoprotein induced by free radicals

The oxidative modification of low density lipoprotein (LDL) is accepted to be an important early event of atherosclerosis, but it has not yet been well understood. The preventive effects of two antioxidants with different functions, ebselen and probucol, against the oxidative modification of LDL induced by copper or a water-soluble radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) were studied in order to elucidate the mechanism of modification of apolipoprotein B-100 (apoB). Ebselen inhibited the copper-induced oxidation completely by reducing the hydroperoxides in LDL, since the initiation of copper-dependent oxidation requires the presence of a trace amount of hydroperoxides in LDL. On the other hand, ebselen did not suppress the oxidations of LDL induced by AAPH which generated free radicals by its thermal decomposition. The AAPH-induced oxidation of LDL in the absence of ebselen gave phosphatidylcholine hydroperoxide and cholesteryl ester hydroperoxide as major products, while in its presence, the hydroperoxides were reduced to corresponding alcohols. Interestingly, ebselen had little effect on the increase of relative electrophoretic mobility and fragmentation of intact apoB in the AAPH-induced oxidation. Probucol inhibited the oxiation of lipids in LDL effectively induced by either copper or AAPH, but the protein modifications were observed even in the presence of probucol. It was suggested that (1) lipid hydroperoxides do not play an important role in the modification of apoB such as increase in negative charge and fragmentation, (2) the direct attack of free radicals upon apoB and its modification by lipid oxidation products derived from hydroperoxides increase the negative charge of apoB, and (3) its fragmentation is caused primarily by an attack of free radicals.