linoleic-acid-hydroperoxide and 2-2-5-7-8-pentamethyl-1-hydroxychroman

The protective effects of phenolic antioxidants on linoleic acid hydroperoxide (LOOH)-induced toxicity to cultured human umbilical vein endothelial cells were examined. Our previous results were confirmed that for tocopherol homologs, lipophilicity and the presence of a phenolic hydroxyl group and two alkyl groups at its ortho positions are critical for protection against LOOH-induced cytotoxicity. Probucol and butylated hydroxytoluene (BHT) were more effective than other simple alkylated phenols. It was found that the protective effects of alkylated phenols were depended on by the presence of two alkyl groups; in particular, two tert-butyl groups, at positions ortho to a hydroxyl group and an alkyl group at the para position. Among alpha-tocopherol, 2,2,5,7,8-pentamethylchroman-6-ol, and BHT, the relative effectiveness of protection against the cytotoxicity (1.0:0.86:0.58, respectively) was inconsistent with the previously reported, relative antioxidant activity in homogeneous solution (1.0:1.2:0.004, respectively). Probably, the effectiveness of protection by phenolic antioxidants against the cytotoxicity depend primarily on their incorporation rate into cells due to their lipophilicity, secondly on their antioxidant activity, and thirdly on their orientation in biomembranes.

Topics: Antioxidants; Butylated Hydroxytoluene; Cell Survival; Cells, Cultured; Chromans; Endothelium, Vascular; Free Radicals; Humans; Linoleic Acids; Lipid Peroxides; Phenols; Probucol; Structure-Activity Relationship; Vitamin E

The protective effects of vitamin E (alpha-tocopherol) and its model compounds, which act as antioxidants, on linoleic acid hydroperoxide-induced injury to human umbilical vein endothelial cells were examined. When incubated at 50 microM with endothelial cells at 37 degrees C for 24 hr, alpha-tocopherol protected the cells from injury, and 2,2,5,7,8-pentamethylchroman-6-ol showed a similar protective effect. Trolox C, a water-soluble vitamin E model compound, had no protective effect. Tocol, a poor antioxidant, proved toxic. During preincubation, alpha-tocopherol was incorporated into the cells at 16.6 nmol/mg protein, while the pentamethylchromanol was incorporated at 0.5 nmol/mg protein; Trolox C was not incorporated at all. The results suggest that agents having both high antioxidant activity and lipophilicity can protect endothelial cells from linoleic acid hydroperoxide-induced injury.

Topics: Antioxidants; Cell Survival; Cells, Cultured; Chromans; Dose-Response Relationship, Drug; Endothelium, Vascular; Humans; Kinetics; Linoleic Acids; Lipid Peroxides; Umbilical Veins; Vitamin E