Free radicals, oxidative stress, and antioxidants in human health and disease

Abstract

Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body. Free-radical mechanisms have been implicated in the pathology of several human diseases, including cancer, atherosclerosis, malaria, and rheumatoid arthritis and neurodegenerative diseases. For example, the superoxide radical (O₂ ^·-) and hydrogen peroxide (H₂O₂) are known to be generated in the brain and nervous system in vivo, and several areas of the human brain are rich in iron, which appears to be easily mobilizable in a form that can stimulate free-radical reactions. Antioxidant defenses to remove O₂ ^·- and H₂O₂ exist. Superoxide dismutases (SOD) remove O₂ ^·- by greatly accelerating its conversion to H₂O₂. Catalases in peroxisomes convert H₂O₂ into water and O₂ and help to dispose of H₂O₂ generated by the action of the oxidase enzymes that are located in these organelles. Other important H₂O₂-removing enzymes in human cells are the glutathione peroxidases. When produced in excess, ROS can cause tissue injury. However, tissue injury can itself cause ROS generation (e.g., by causing activation of phagocytes or releasing transition metal ions from damaged cells), which may (or may not, depending on the situation) contribute to a worsening of the injury. Assessment of oxidative damage to biomolecules by means of emerging technologies based on products of oxidative damage to DNA (e.g., 8-hydroxydeoxyguanosine), lipids (e.g., isoprostanes), and proteins (altered amino acids) would not only advance our understanding of the underlying mechanisms but also facilitate supplementation and intervention studies designed and conducted to test antioxidant efficacy in human health and disease.

Keywords: 8-hydroxydeoxyguanosine; Antioxidants; DNA damage; atherosclerosis; flavonoids; free radicals; isoprostanes; lipid peroxidation; oxidative protein damage; oxidative stress; phytochemicals.