Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-kappa B activation

Oxidative modification of LDL has been recognized as playing an important r ole 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 endothe lial cells (EC), Lactate dehydrogenase (LDH) release as an index of membran e damage, methylthiazol tetrazoium (MTT) assay for cell viability and thiob arbituric acid reactive substances (TBARS) indicating lipid peroxidation we re measured. Ox-LDL caused an increase of LDH release, loss of cell viabili ty and TEARS formation. Both AGE and SAC prevented all of these changes. To elucidate the mechanism, effects of AGE or SAC on intracellular glutathion e (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 h ydrogen peroxide (H2O2) or tumor necrosis factor (TNF)-alpha -induced nucle ar factor (NF)-kappaB activation were determined. Pretreatment of EC with S AC inhibited NF-kappaB activation. We demonstrated that both AGE and SAC ca n protect EG from Ox-LDL-induced injury by preventing intracellular GSH dep letion in EC and by minimizing release of peroxides from EC and M Phi. SAC also inhibited H2O2- or TNF-alpha -induced NF-kappaB activation. Our data s uggest that AGE and its main compound, SAG, may be useful for prevention of atherosclerosis.