Probucol prevents oxidative injury to endothelial cells.
We evaluated the effect of the antioxidant, probucol, on the cytotoxic effects of oxidized low density lipoprotein (OX-LDL) or of cumene hydroperoxide (CumOOH) on cultured bovine endothelial cells (EC). The addition of CumOOH to EC caused the release of lactate dehydrogenase and the accumulation of thiobarbituric acid-reacting substances (TBARS), effects that were protected against by preincubation with either probucol or tocopherol. Similarly, preincubation of EC with those antioxidants protected against OX-LDL toxicity and the accumulation of TBARS. The content of probucol in EC measured by high performance liquid chromatography was directly correlated with the extent of protection against OX-LDL toxicity. We also found that treatment of EC with serum from patients receiving treatment with probucol resulted in the detection of probucol in the cells. We conclude that probucol is transported and incorporated into EC membranes to act as a radical-trapping antioxidant, protecting the EC against oxidative stress. Our results also indicate that lipid peroxidation in cellular membranes involves cell injury inflicted by OX-LDL.
Kuzuya
M
M
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Naito
M
M
Funaki
C
C
Hayashi
T
T
Asai
K
K
Kuzuya
F
F
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000037:antagonists & inhibitors / Q000633:toxicity; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000633:toxicity; D010084:Oxidation-Reduction; D011341:Probucol / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001555:Benzene Derivatives; D008077:Lipoproteins, LDL; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D011341:Probucol; C007164:cumene hydroperoxide