Anti- and pro-oxidative effects of flavonoids on metal-induced lipid hydroperoxide-dependent lipid peroxidation in cultured hepatocytes loaded with alpha-linolenic acid

Lipid hydroperoxide (LOOH)-dependent lipid peroxidation was induced in oc-l inolenic acid (LNA)-loaded hepatocytes by adding Fe, Cu, V, or Cd ions at c oncentrations from 20 to 500 mu M. The effects of structurally related flav onoids at concentrations from 10 to 500 mu M on the lipid peroxidation were examined. The results with regard to each flavonoid subclass are as follow s: (i) Flavonols such as myricetin, quercetin, fisetin, and kaempferol, but not morin, showed dose-dependent antioxidative activity against metal-indu ced lipid peroxidation at all metal concentrations. Myricetin, quercetin, a nd fisetin were the most effective antioxidants, although their efficacies depended on the metal ion. Kaempferol and morin had antioxidative activity equal to the other flavonols in the presence of Cu ions, but were much less effective for the other three metal ions. (ii) Flavones, luteolin, apigeni n, and chrysin were antioxidative at low Fe concentrations, but were pro-ox idative at high Fe concentrations. Luteolin exhibited antioxidative activit y similar to that of catechol-containing flavonols in the presence of the o ther three metal ions. Apigenin and chrysin also acted as pro-oxidants with V or with all metal ions, respectively. (iii) Taxifolin, a flavanone, also showed both anti- and prooxidative activity, depending on Fe concentration s, but with other metal showed only antioxidative activity ions. (iv) Epiga llocatechin, a flavanol, was antioxidative with all metal ions, and its act ivity was similar to that of catechol-containing flavonols. The various eff ects of flavonoids on metal-induced lipid peroxidation in LNA-loaded hepato cytes is discussed with regard to the change in redox potential of flavonoi d-metal complexes. (C) 1999 Elsevier Science Inc.