Low-density lipoproteins oxidized by ultraviolet radiations constitute a useful model system for studying their cytotoxic effect on cultured cells. Polyphenolic flavonoids were able to inhibit the peroxidation of low-density lipoproteins (IC50; 10-20 microM for quercetin or rutin) and their subsequent cytotoxicity. The inhibition of the cytotoxic effect was well correlated with that of TBARS formation. Our most important and novel conclusion is that quercetin and rutin are able to prevent directly at the cellular level the cytotoxic effect of oxidized LDL, since cells preincubated with polyphenolic flavonoids were protected against the cytotoxic effect of previously oxidized low-density lipoprotein (IC50; 0.1 and 3 microM with quercetin and rutin, respectively). In contrast, flavone was completely inefficient. In conclusion polyphenolic flavonoids can protect cells against the injury due to oxidation of low-density lipoproteins by constituting two lines of defence: (1) at high concentrations, antioxidant effect inhibiting the lipoprotein oxidation and the subsequent cytotoxicity; (2) at low concentrations, direct protection of cells against the cytotoxic effect of oxidized low-density lipoproteins.