**3. Role of Antioxidants in the Brain**

Antioxidants act in two ways: First, the antioxidant defense systems, which are initiated against oxidative damage, prevent generation of ROS, and block and capture the generated radicals [39]. These systems are present in the aqueous and membrane compartments of cells; they can be enzymatic or non-enzymatic. The first line of defense has been identified as an enzymatic antioxidant system that includes superoxide dismutase, catalase, and glutathione peroxidase. The second line of defense is represented by reduced thiol and non-enzymatic antioxidants, including hydro- and lipo-soluble or metabolic compounds [7]. Second, during the antioxidant repair process, the removal of damaged biomolecules before their aggregation causes alterations in cell metabolism. The intervention by the repair systems consists of repairing oxidatively damaged nucleic acids by specific enzymes, removing oxidized proteins by the proteolytic systems, and repairing oxidized lipids by phospholipases, peroxidases, or acryl transferases [8,39,40].

Antioxidants act to directly scavenge oxidizing radicals and regenerate oxidized biomolecules in organisms. Neuronal cells possess several factors that minimize oxidative damage and a complex antioxidant system consisting of various antioxidant enzymes and non-enzymes. With regard to the mechanism of action of antioxidants, antioxidants respond to different steps of oxidative radical processing and can be considered by taking into account the different steps of lipid peroxidation in cell membranes such as: initiation, propagation, and chain termination [36]. The first step of initiation of lipid peroxidation can be promoted by diverse exogenous factors, endogenous enzyme systems, and the electron transport chain in the mitochondria. The propagation step of peroxidation is initiated by the addition of oxygen to carbon-centered radicals, which are generated at, or near, the diffusion-controlled rate. Propagation is represented by the transfer of a hydrogen atom to the chain carrying peroxyl radicals and occurs at a relatively slow rate. Antioxidants can inhibit lipid peroxidation by removing molecular oxygen or by decreasing the local concentration of molecular oxygen, removing pro-oxidative metal ions, trapping aggressive ROS, scavenging chain initiating radicals, breaking the chain of free radical reactions, and quenching singlet oxygen [7,41]. In its protective role, enzymatic antioxidants are chain-breaking antioxidants which are able to scavenge radical species while non-enzymatic antioxidants are singlet oxygen quenchers, metal chelators, oxidative enzyme inhibitors, peroxide decomposers, and/or ultra violet (UV) radiation absorbers [7]. Additionally, antioxidant enzymes can catalyze the synthesis or regeneration of non-enzymatic antioxidants.
