LDL-induced cytotoxicity and its inhibition by anti-oxidant treatment in cultured human endothelial cells and fibroblasts.

Low density lipoproteins (LDL) isolated by ultracentrifugation induce cytotoxic changes in cultured human endothelial cells (EC) and fibroblasts if the ratio between LDL cholesterol and the final protein concentration of the culture medium exceeds 0.10-0.12 mmol/g protein. In order to investigate if reactive oxygen species could contribute to the cytotoxicity, LDL were prepared in the presence of the antioxidants butylated hydroxytoluene (BHT) or superoxide dismutase (SOD), while routinely prepared LDL from the same donors served as control (N-LDL). A radiochromium release assay was used to evaluate cellular injury. BHT treatment of the LDL fraction virtually abolished LDL-induced cytotoxicity in cultured human EC and fibroblasts. SOD-LDL offered partial protection against LDL cytotoxicity. A positive correlation between the cytotoxicity of the various fractions and their content of malondialdehyde (MDA) further supports our conclusion that lipid peroxides in the LDL fractions mediate the cytotoxic effect on cultured cells.