Tamoxifen, esterified estradiol, and physiologic concentrations of estradiol inhibit oxidation of low-density lipoprotein by endothelial cells

OBJECTIVE: We investigated the antioxidant effect of tamoxifen, esterified estradiol, and physiologic concentrations of 17 beta -estradiol on endothel ial cell-mediated oxidation of low-density lipoprotein. STUDY DESIGN: Human umbilical vein endothelial cells were preincubated with nanomolar concentrations of estradiol, estradiol stearate, and tamoxifen. Low-density lipoprotein was isolated and incubated with cells in serum-free medium. Oxidation of low-density lipoprotein was quantified after 8, 16, a nd 24 hours of incubation as the formation of thiobarbituric acid-reactive substances. RESULTS: Compared with control, preincubation of human umbilical vein endot helial cells with 1- or 10-nmol/L estradiol resulted in a 12% reduction in the formation of thiobarbituric acid-reactive substances at 24 hours. Prein cubation of human umbilical vein endothelial cells with either 10-nmol/L es tradiol 17-stearate or 10-nmol/L tamoxifen resulted in 26% and 20% decrease s, respectively, in formation of thiobarbituric acid-reactive substances at 24 hours. The difference in the reduction in thiobarbituric acid-reactive substances between control and treatment wells became more pronounced over time. CONCLUSION: Under these experimental conditions, tamoxifen, esterified estr adiol, and physiologic concentrations of exogenous estradiol inhibit oxidat ion of low-density lipoprotein by human umbilical vein endothelial cells.