Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-kappa b activation.
Oxidative modification of LDL has been recognized as playing an important role in the initiation and progression of atherosclerosis. In this study, we determined the effects of aged garlic extract (AGE) and its major compound, S-allylcysteine (SAC), on oxidized LDL (Ox-LDL)-induced injury in endothelial cells (EC). Lactate dehydrogenase (LDH) release as an index of membrane damage, methylthiazol tetrazoium (MTT) assay for cell viability and thiobarbituric acid reactive substances (TBARS) indicating lipid peroxidation were measured. Ox-LDL caused an increase of LDH release, loss of cell viability and TBARS formation. Both AGE and SAC prevented all of these changes. To elucidate the mechanism, effects of AGE or SAC on intracellular glutathione (GSH) level in EC, and release of peroxide from EC and macrophages (M Phi) were determined. Ox-LDL depleted intracellular GSH and increased release of peroxides. Both AGE and SAC inhibited these changes. Effects of SAC on hydrogen peroxide (H(2)O(2)) or tumor necrosis factor (TNF)-alpha-induced nuclear factor (NF)-kappa B activation were determined. Pretreatment of EC with SAC inhibited NF-kappa B activation. We demonstrated that both AGE and SAC can protect EC from Ox-LDL-induced injury by preventing intracellular GSH depletion in EC and by minimizing release of peroxides from EC and M Phi. SAC also inhibited H(2)O(2)- or TNF-alpha-induced NF-kappa B activation. Our data suggest that AGE and its main compound, SAC, may be useful for prevention of atherosclerosis.
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Department of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005737:Garlic / Q000737:chemistry*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010946:Plants, Medicinal
D000975:Antioxidants; D008077:Lipoproteins, LDL; D016328:NF-kappa B; C065299:S-allylcysteine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D003545:Cysteine