Aged garlic extract attenuates intracellular oxidative stress

Oxidation of low density lipoprotein (LDL) has been recognized as playing a n important role in the initiation and progression of atherosclerosis. We r ecently reported that aged garlic extract (AGE) inhibited LDL oxidation and minimized oxidized LDL-induced cell injury. In this study, the antioxidant effects of AGE were further examined using bovine pulmonary artery endothe lial cells (PAEC) and murine macrophages. Lactate dehydrogenase (LDH) relea se, as an index of membrane injury and intracellular glutathione (GSH) leve ls were determined. Oxidized LDL (Ox-LDL) caused an increase of LDH release and depletion of GSH. Pretreatment with AGE prevented these changes. AGE e xhibited an inhibition of Ox-LDL-induced peroxides in PAEC. AGE suppressed peroxides in murine Macrophage (J774 cells) dose-dependently. The J774 cell s were also incubated with AGE, interferon-gamma (IFN-gamma) and lipopolysa ccharide (LPS) and nitric oxide (NO) production was measured. AGE inhibited NO production in J774 cells. In a cell free system, AGE was shown to scave nge H2O2 dose-dependently. Our data demonstrate that AGE can protect the en dothelial cells from oxidized LDL-induced injury by preventing depletion of intracellular GSH and by removing peroxides. AGE also reduces levels of NO and peroxides in macrophages. These data suggest that AGE is a useful prot ective agent against cytotoxicity associated with Ox-LDL and NO, and it may thus be useful for the prevention of atherosclerosis and cardiovascular di seases.