Influence of prenylated and non-prenylated flavonoids on liver microsomal lipid peroxidation and oxidative injury in rat hepatocytes

Prenylated chalcones from hops and beer were compared with non-prenylated f lavonoids [chalconaringenin (CN), naringenin (NG), genistein (GS) and querc etin (QC)] for their ability to inhibit lipid peroxidation in rat liver mic rosomes. Chalcones with prenyl- or geranyl-groups (5 and 25 muM) were more effective inhibitors of microsomal lipid peroxidation than CN, NG or GS ind uced by Fe2+/ascorbate. Prenylated chalcones were effective inhibitors of m icrosomal lipid peroxidation induced by Fe3+-ADP/NADPH and by tert-butyl hy droperoxide (TBH) but to a lesser extent compared to the Fe2+/ascorbate sys tem. An increase of prenyl substituents decreased antioxidant activity in t he lipid peroxidation systems. Certain flavonoids behaved as prooxidants in the iron-dependent lipid peroxidation systems. For example, at 5 muM, NG e nhanced iron/ascorbate-induced lipid peroxidation whereas CN, diprenylxanth ohumol and tetrahydroxanthohumol enhanced Fe3+-ADP/NADPH-induced lipid pero xidation. None of the flavonoids (25 muM), except QC, inhibited NADPH cytoc hrome P450-reductase activity of rat liver microsomes, suggesting that the mechanism of inhibition of lipid peroxidation induced by Fe3+-ADP/NADPH is not due to inhibition of the reductase enzyme. Chalcones exhibiting antioxi dant activity against TBH-induced lipid peroxidation such as xanthohumol an d 5'-prenylxanthohumol, and NG, with no antioxidant property at 5 muM conce ntration protected cultured rat hepatocytes from TBH toxicity. Other antiox idants (desmethylxanthohumol and CN) in the TBH system were not cytoprotect ive. These results demonstrate the importance of prenyl groups in the antio xidant activity of hop chalcones in the various in vitro systems of lipid p eroxidation. Furthermore, the antioxidant activity of the flavonoids has li ttle or no bearing on their ability to protect rat hepatocytes from the tox ic effects of TBH. (C) 2001 Elsevier Science Ltd. All rights reserved.