Protection of linoleic acid hydroperoxide-induced cytotoxicity by phenolic antioxidants.
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.
Kaneko
T
T
Tokyo Metropolitan Institute of Gerontology, Itabashiku, Japan.
Kaji
K
K
Matsuo
M
M
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries; D005609:Free Radicals; D006801:Humans; D008041:Linoleic Acids / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D011341:Probucol / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D002839:Chromans; D005609:Free Radicals; D008041:Linoleic Acids; D008054:Lipid Peroxides; D010636:Phenols; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; C008285:linoleic acid hydroperoxide; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; D011341:Probucol