Oxidative modification of DNA, proteins, lipids and small cellular molecules by reactive oxygen species (ROS) plays a role in a wide range of common diseases and age-related degenerative conditions.
These include cardiovascular disease, inflammatory conditions, and neurodegenerative diseases such as Alzheimer's disease, mutations and cancer.
Oxidant damage by ROS is linked to photoaging, radiation toxicity, cataract formation and macular degeneration; it is implicated in ischemia/reperfusion tissue injury and thought to play a role in decreased function of some immune cells.
Antioxidants, including those in AGE, which protect against oxidative damage lower the risk of injury to vital molecules and to varying degrees may help prevent the onset and progression of disease.
Sources of ROS
ROS include free radicals and nonradical species.
The free radicals carry an unpaired electron and are unstable and reactive.
They include superoxide, nitric oxide and the most reactive and toxic ROS, the hydroxyl radical.
Nonradical oxidants include hydrogen peroxide, singlet oxygen and ozone, which form free radicals in tissues through various chemical reactions.
Most of the ROS produced by cells come from the following four sources: 1) normal aerobic respiration in mitochondria, which generates superoxide radical (O2-) and the ensuing toxic products, hydrogen peroxide (H2O2) and the highly reactive hydroxyl radical (OH·); 2) stimulated macrophages and polymorphonuclear leukocytes, which release superoxide and the nitric oxide radical (NO·), which in turn can interact to form the nonradical destructive peroxynitrite; 3) peroxisomes, cell organelles that produce H2O2 as a by-product of degrading fatty acid and other molecules; and 4) oxidant by-products that occur during the induction of cytochrome P450 enzymes.
Exogenous sources of ROS include the following: tobacco smoke, which has a broad spectrum of oxidant-ionizing radiation, which generates free radicals in exposed tissues, notably the highly reactive OH· radical; UV light, which produces singlet oxygen (1O2) and OH; ozone (O3) and oxides of nitrogen in polluted air; industrial toxins such as carbontetrachloride; drugs such as phenobarbital, which is a known tumor promoter in liver; and charcoal-broiled foods, which form a variety of carcinogens, notably benzo(a)pyrene.
Endogenous levels of ROS, which endanger our health, increase during chronic infection and inflammation, strenuous physical exercise, hypermetabolic states seen in stress, trauma and sepsis, and during exposure to exogenous sources.
To protect molecules against toxic free radicals and other ROS, cells have developed antioxidant defenses that include the enzymes superoxide dismutase (SOD), which dismutates superoxide; catalase and glutathione peroxidase, which destroy toxic peroxides, and small molecules including glutathione.
External sources of antioxidant nutrients that are essential for antioxidant protection include antioxidant vitamins C and E, vitamin A/provitamin A and the mineral selenium, a component of selenium-dependent glutathione peroxidase.
Phytochemicals from plant-rich diets, including garlic, provide important additional protection against oxidant damage.
The variety of antioxid ant phytochemicals in AGE, which protect against disease-causing oxidative damage, may act in single and combined fashion.
Antioxidant actions of AGE
Scavenging ROS, inhibiting LDL oxidation and lipid peroxide formation.
The antioxidative actions of AGE and its components are determined by their ability to scavenge ROS and inhibit the formation of lipid peroxides.
These effects are determined by measuring the decrease in ROS-induced chemiluminescence, inhibition of thiobarbituric acid reactive substances (lipid peroxides) (TBARS assay), and in vitro inhibition of the release of pentane, a product of oxidized lipids, in the breath of an animal exposed to oxidative stress.
Oxidized LDL promotes vascular dysfunction, which contributes to atherosclerosis, in part by its cytotoxic effects on endothelial cells.
Using an in vitro system of endothelial cells exposed to oxidant copper ions, AGE and SAC were shown to scavenge ROS, inhibit oxidation of LDL and inhibit endothelial cells injury by oxidized LDL.
AGE has been shown to inhibit lipid peroxide formation in several studies.
In one study, TBARS induced by hydrogen peroxidewere inhibited 31-89% by AGE and 33-67% by SAC in a concentration-dependent manner, thus mitigating oxidation events, which are implicated in the formation of atherogenic lesions.
An additional assay, the 1,1-diphenyl-2-picryl-hydrazine assay, showed the antioxidant effects of allixin, SAC, SMAC and diallyl polysulfides, whose radical-scavenging action increased with the number of sulfur atoms.
More recently, other components of AGE, N-fructosyl arginine and N-fructosyl glutamate, showed antioxidant effects by spinresonance spectroscopy.