Figure 4.

Mechanisms of oxidative stress are targets of antioxidant dietary compounds. (a) Oxidative stress occurs when there is an imbalance between ROS and antioxidant defence mechanisms. ROS target biomolecules such as DNA, proteins and lipids and impart oxidative damage which underlies many diseases. (b) Natural antioxidants such as vitamin C, vitamin A, EGCG, and genistein can neutralize free radicals by donating an electron, thus inhibiting oxidative DNA damage. Lipid soluble antioxidants, vitamin E, and curcumin prevent lipid peroxidation by quenching free radicals and protecting polyunsaturated fatty acids (PUFAs) from peroxidation. (c) The interconnection of vitamin E, vitamin C, and GSH reductase (GR) is shown, demonstrating the function of regeneration of antioxidants when oxidized. Vitamin C regenerates the reduced form of vitamin E which utilizes GR to convert GSSG to its reduced form, GSH. EGCG promotes cellular redox balance through increasing the activity of GSH. (d) SOD catalyses the reduction of superoxide anion (O₂ ^•−) to hydrogen peroxide (H₂O₂), which is subsequently neutralized into water and oxygen by GSH peroxidase (GPx) and/or catalase (CAT). Antioxidants including resveratrol (RSV), EGCG, and selenium (Se) enhance the activity of specific antioxidant enzymes (SOD, CAT, and GPx) to contribute to alleviation of oxidative stress. Additionally, genistein scavenges H₂O₂ and free radicals leading to inhibition of H₂O₂‐induced oxidative damage. (e) Three isoforms of NOS, iNOS, eNOS, and nNOS (inducible, endothelial, and neuronal) can generate NO. NO can act as a signalling molecule or it can react with superoxide anion (O₂ ^•−) generating peroxynitrite anion (ONOO⁻), which is a highly reactive nitrogen species. Thus, ONOO⁻ can trigger oxidation of DNA, proteins and lipids. Antioxidants such as curcumin and resveratrol promote redox balance by targeting NO and ONOO⁻ concentration respectively. (F) Cellular oxidative stress caused by generation of ONOO⁻ and O₂ ^•− stimulates nuclear factor erythroid 2‐related factor 2 (Nrf2) to dissociate from its repressor protein (Keap1) and translocate from cytoplasm into the nucleus to bind to antioxidant response elements (AREs) and activate transcription of antioxidant‐related genes. Natural antioxidants shown in the grey box have been shown to activate Keap1‐Nrf2 pathway. (g) Table of major contributors to oxidative stress in each chronic disease