Aged garlic extract attenuates intracellular oxidative stress.
Oxidation of low density lipoprotein (LDL) has been recognized as playing an important role in the initiation and progression of atherosclerosis. We recently 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 endothelial cells (PAEC) and murine macrophages. Lactate dehydrogenase (LDH) release, as an index of membrane injury, and intracellular glutathione (GSH) levels were determined. Oxidized LDL (Ox-LDL) caused an increase of LDH release and depletion of GSH. Pretreatment with AGE prevented these changes. AGE exhibited an inhibition of Ox-LDL-induced peroxides in PAEC. AGE suppressed peroxides in murine Macrophage (J774 cells) dose-dependently. The J774 cells were also incubated with AGE, interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) and nitric oxide (NO) production was measured. AGE inhibited NO production in J774 cells. In a cell free system, AGE was shown to scavenge H2O2 dose-dependently. Our data demonstrate that AGE can protect the endothelial 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 protective agent against cytotoxicity associated with Ox-LDL and NO, and it may thus be useful for the prevention of atherosclerosis and cardiovascular diseases.
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Department of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, CA, USA.
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BH
D000818:Animals; D002417:Cattle; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005737:Garlic / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal
D008077:Lipoproteins, LDL; D010936:Plant Extracts; C099252:oxidized low density lipoprotein; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione