Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid.

Low density lipoprotein (LDL) has been reported to be injurious or toxic to cells in vitro. This injurious effect is, in some instances, due to oxidation of the lipid moiety of the lipoprotein. The objectives of this study were to determine if the oxidation rendering the lipoprotein toxic to human skin fibroblasts occurred by free radical mechanisms, and if so, which of the common free radical oxygen species were in- volved. The selective free radical blockers or scavengers em- ployed included superoxide dismutase for superoxide, catalase for hydrogen peroxide, dimethylfuran for singlet molecular oxygen, and mannitol for hydroxyl radical. The presence dur- ing lipoprotein preparation of general free radical scavengers (vitamin E, butylated hydroxytoluene) or the divalent cation chelator ethylenediamine tetraacetic acid prevented the for- mation of cytotoxic low density lipoprotein, while the simul- taneous presence of superoxide dismutase and catalase par- tially inhibited its formati0n.l The results indicate that su- peroxide and/or hydrogen peroxide are involved in the formation of the toxic LDL lipid. The toxic action of oxidized LDL could not be prevented by inclusion of antioxidants in the culture medium, indicating that an oxidized lipid was re- sponsible for cell injury rather than free radicals generated in culture by the action of oxidized LDL. Three separate assays for cell injury (enumeration of attached cells, cell loss of lactate dehydrogenase into the culture medium, and trypan blue up- take) indicated a sequence of events in which the fibroblasts are injured, die, and then detach.-Morel, D. W., J. R. Hes- der, and G. M. Chisolm. Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid. J. Lipid Res. 1983. 24: 1070-1076.