Abstract
Effect of exogenously added antioxidants on the activity of the mouse macrophage scavenger receptors for oxidized low density lipoprotein (oxLDL) was investigated. Binding of oxLDL-coated erythrocytes and/or 125I-oxLDL to a monolayer of thioglycollate-induced peritoneal macrophages preincubated with antioxidants at 37°C for 2 h was examined. The binding was effectively or slightly decreased by preincubation of macrophages with probucol, butylated hydroxytoluene, α-tocopherol, sesamol, propyl gallate, quercetin, nordihydroguaiaretic acid, epicatechin gallate, epigallocatechin gallate (EGCg), glutathione isopropyl ester (GSH-Pr), N-acetylcysteine, ascorbic acid, erythorbic acid, and Desferal at concentrations lower than 100 μM. The binding was slightly enhanced by preincubation of macrophages with buthionine sulfoximine. The antioxidants and related compounds inhibited the formation of foam cells induced by oxLDL in the prolonged incubation for 24 h. Glutathione, oxidized glutathione and dehydroascorbic acid inhibited the foam cell formation, Total cholesterol accumulation induced by oxLDL in the prolonged incubation was reduced by the phenolic antioxidants. The number of scavenger receptors of macrophages was unchanged upon treatment with EGCg and GSH-Pr. The results indicate that the antioxidants at relatively high concentrations inhibited macrophage functions, binding of oxLDL, foam cell formation, and accumulation of cholesterol, and suggest that the scavenger receptor activity of macrophages was exerted by certain oxidative mechanisms.