Antioxidant Therapy and its Effectiveness in Oxidative Stress‐Mediated Disorders

Abstract

Antioxidants are chemical compounds that give an electron to free radical molecules and convert them into a harmless configuration. This prevents damage to chain reaction and can involve lipids, proteins, enzymes, carbohydrates, DNA, cell, and nuclear membranes up to the death of the cell. When the body’s scavenging ability is not able to deal with free radical species, that is, reactive oxygen species (ROS) and reactive nitrogen species (RNS), they cause oxidative damage in all the body’s tissues, leading to disease. The effect of oxidative stress at the cellular level is illustrated in Figure 15.1. This oxidation-induced damage may be prevented by exogenous or endogenous antioxidants. ROS seem to be an important factor involved in endothelial dysfunction, diabetes, atherosclerosis, and ischemia, while RNS have been associated with arthritis, diabetes, degenerative neuronal diseases, cancer, and atherosclerosis. Under physiological conditions, the overproduction of ROS and RNS and their neutralization are prevented by the activity of the endogenous antioxidative defense system (AOS). It includes enzymes like superoxide dismutase, catalase, glutathione peroxidase, and other antioxidant regenerating enzymes such as glutathione reductase, dehydroascorbate reductase, and glucose-6 phosphate dehydrogenase that maintains reduced NADPH, hydrophilic scavengers like urate ascorbate glutathione, flavonoids, and lipophilic scavengers, like tocopherols, carotenoids, and ubiquinone. Antioxidants are generally supplied in the diet and include polyphenols, lipoic and ascorbic acid, carotenoids, resveratrol, epigallocathechin-3-0-gallate, lycopene, quercetin, genistein, ellagic acid, ubiquinone, and indole-3 carbinole. The properties of these compounds are involved in the physiological redox balance as they can prevent damage to the tissues due to the oxidation typical of all the biological systems and characterized by the production of highly reactive free radicals [1]. There is growing evidence that ROS play a key role in several pathological conditions and in the aging process. No final conclusion about possible therapy protocols based on the administration of antioxidant compounds has been reached yet, but it can be hypothesized that, in the near future, biochemical investigations, able to detect an oxidative imbalance, may become routine tests necessary to restore the antioxidant natural protective barrier, avoiding irreversible damage. An example of the power of antioxidant supplementation to prevent excessive oxidative stress is given by a study conducted in 400 healthy subjects to assess the effect of physical activity combined with antioxidant treatment (330 ml/day of Funcionat). This study shows that, after 10 months, the oxidative stress caused by exercise was prevented by the antioxidant treatment [2]. There is also a lack of agreement concerning the parameters of oxidative stress or antioxidant state in specific