PMID- 9568736 OWN - NLM STAT- MEDLINE DCOM- 19980611 LR - 20240109 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 137 IP - 1 DP - 1998 Mar TI - The antioxidative effects of the isoflavan glabridin on endogenous constituents of LDL during its oxidation. PG - 49-61 AB - The effect of the consumption of glabridin, an isoflavan isolated from Glycyrrhiza glabra (licorice) root, on the susceptibility of low density lipoprotein (LDL) to oxidation was studied in atherosclerotic apolipoprotein E deficient (E[o] mice) and was compared with that of the known flavonoids, quercetin and catechin. Glabridin inhibitory activity on in vitro oxidation of human LDL was also investigated by determining the formation of lipid peroxides and oxysterols and the consumption of LDL-associated lipophilic antioxidants. Determination of the extent of LDL oxidation by measuring the formation of thiobabituric acid reactive substances (TBARS) after 2 h of LDL incubation with CuSO4 (10 microM) or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) (5 mM), revealed that glabridin or quercetin consumption resulted in a 53 and 54% reduction in copper ion induced oxidation, respectively, and a 95 and 83% reduction in AAPH induced LDL oxidation, respectively. No inhibition was obtained with consumption of catechin. About 80% of glabridin was found to bind to the LDL human particle. In the in vitro oxidation of LDL induced by AAPH (5 mM), glabridin inhibited the formation of TBARS, lipid peroxides and cholesteryl linoleate hydroperoxide (CLOOH) at all the concentrations tested (5-60 microM), while in oxidation induced by copper ions (10 microM), glabridin exhibited a pro-oxidant activity at concentrations lower than 20 microM, and a clear antioxidant activity at concentrations greater than 20 microM. Glabridin (30 microM) inhibited the formation of cholest-5-ene-3,7-diol (7-hydroxycholesterol), cholest-5-ene-3-ol-7-one (7-ketocholesterol) and cholestan-5,6-epoxy-3-ol (5,6-epoxycholesterol) after 6 h of AAPH induced LDL oxidation, by 55, 80 and 40%, respectively, and after 6 h of copper ion induced LDL oxidation, by 73, 94 and 52%, respectively. Glabridin also inhibited the consumption of beta-carotene and lycopene by 38 and 52%, respectively, after 0.5 h of LDL oxidation with AAPH, but failed to protect vitamin E. The in vivo and in vitro reduction of the susceptibility of LDL to oxidation obtained with glabridin, may be related to the absorption or binding of glabridin to the LDL particle and subsequent protection of LDL from oxidation by inhibiting the formation of lipid peroxides and oxysterols, and by protecting LDL associated carotenoids. FAU - Belinky, P A AU - Belinky PA AD - Laboratory of Natural Compounds for Medical Use, Migal, Galilee Technological Center, Kiryat Shmona, Israel. FAU - Aviram, M AU - Aviram M FAU - Fuhrman, B AU - Fuhrman B FAU - Rosenblat, M AU - Rosenblat M FAU - Vaya, J AU - Vaya J LA - eng PT - Journal Article PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Amidines) RN - 0 (Antioxidants) RN - 0 (Chelating Agents) RN - 0 (Flavones) RN - 0 (Flavonoids) RN - 0 (Free Radical Scavengers) RN - 0 (Isoflavones) RN - 0 (Lipoproteins, LDL) RN - 0 (Oxidants) RN - 0 (Phenols) RN - 0 (Sterols) RN - 01YAE03M7J (beta Carotene) RN - 1406-18-4 (Vitamin E) RN - 36-88-4 (Carotenoids) RN - 7381JDR72F (2,2'-azobis(2-amidinopropane)) RN - 789U1901C5 (Copper) RN - 8R1V1STN48 (Catechin) RN - 9IKM0I5T1E (Quercetin) RN - E1UOL152H7 (Iron) RN - HOC5567T41 (glabridin) RN - S2V45N7G3B (flavone) RN - SB0N2N0WV6 (Lycopene) SB - IM MH - Amidines/antagonists & inhibitors/pharmacology MH - Animals MH - Antioxidants/administration & dosage/*pharmacology MH - Carotenoids/metabolism MH - Catechin/administration & dosage/pharmacology MH - Chelating Agents/administration & dosage/pharmacology MH - Copper/antagonists & inhibitors/pharmacology MH - Dietary Supplements MH - Dose-Response Relationship, Drug MH - Flavones MH - Flavonoids/administration & dosage/pharmacology MH - Free Radical Scavengers/administration & dosage/pharmacology MH - Iron/antagonists & inhibitors MH - Isoflavones MH - Lipid Peroxidation/*drug effects MH - Lipoproteins, LDL/*drug effects/*metabolism MH - Lycopene MH - Mice MH - Mice, Mutant Strains MH - Oxidants/antagonists & inhibitors/pharmacology MH - Oxidation-Reduction/drug effects MH - Phenols/administration & dosage/metabolism/*pharmacology MH - Protein Binding MH - Quercetin/administration & dosage/pharmacology MH - Sterols/metabolism MH - Time Factors MH - Vitamin E/metabolism MH - Vitamin E Deficiency/drug therapy/genetics MH - beta Carotene/metabolism EDAT- 1998/05/06 00:00 MHDA- 1998/05/06 00:01 CRDT- 1998/05/06 00:00 PHST- 1998/05/06 00:00 [pubmed] PHST- 1998/05/06 00:01 [medline] PHST- 1998/05/06 00:00 [entrez] AID - S0021-9150(97)00251-7 [pii] AID - 10.1016/s0021-9150(97)00251-7 [doi] PST - ppublish SO - Atherosclerosis. 1998 Mar;137(1):49-61. doi: 10.1016/s0021-9150(97)00251-7.