Cytoprotective activity against peroxide-induced oxidative damage and cytotoxicity of flavonoids in C6 rat glioma cells

The aim of this study was to investigate the relationship between cytoprotective and cytotoxic activities of selected plant flavonoids in C6 glioma cells. Apigenin, kaempferol, luteolin, and quercetin were cytotoxic at low μM concentrations (LOECs: 5–20 μM), whereas myricetin was less toxic (LOEC > 20 μM). Cytotoxicity was not due to H2O2 generation from flavonoids in culture medium. Quercetin, luteolin, and kaempferol protected the cells from peroxide-induced cytotoxicity. Concentration-effect curves for cytoprotection had a biphasic shape. In contrast, apigenin and myricetin did not exhibit any cytoprotective activity. The first three compounds also inhibited cellular lipid peroxidation induced by CHP, while the latter were ineffective. Importantly, concentrations of luteolin and kaempferol protecting cells under oxidative stress were identical to those causing cell damage under normal conditions. Only in case of quercetin there was a narrow range of concentrations protecting cells without being cytotoxic to non-stressed cells. Thus, even for flavonoids with a high antioxidant capacity in cell-free systems the cytoprotective selectivity (LOECcytotox/LOECcytoprot) was very low or even absent. These results should be taken into account when the prophylactic or therapeutic application of flavonoids as antioxidants is discussed.