The role of reactive oxygen species and antioxidants in dermatology

Abstract

2500 million years ago, oxygen accumulated in the Earth's atmosphere as a result of the evolution of algae capable of photosynthesis. The enormous benefit of oxygen utilization for obtaining energy led to the rapid expansion of aerobic organisms. However, the high reactivity of the oxygen was coupled with the danger of oxidation of important cell components. Roughly 2% of electrons are lost during electron transport in mitochondrial membranes, leading to the formation of reactive oxygen species. Some of these are free radicals, which are defined as atoms or molecules with an unpaired electron, like superoxide anion or the hydroxyl radical. These molecules are extremely chemically reactive and short‐lived. Other reactive molecules such as singlet oxygen and hydrogen peroxide are not free radicals, but are as reactive and capable of initiating oxidative reactions. Together, these molecules are calledreactive oxygen species. Cells have evolved various antioxidant and repair systems for protection against metabolically produced reactive oxygen species. Antioxidant enzymes include superoxide dismutase, catalase, glutathione reductase and glutathione peroxidases, which collectively destroy superoxide, hydrogen peroxide and lipid hydroperoxides. Nonenzymatic small‐molecular‐weight antioxidants are no less important. They build up an effective antioxidant network, which includes glutathione (GSH) and ascorbic acid (vitamin C) in the aqueous phase, and tocopherol (vitamin E) and ubiquinol (coenzyme Q) in the lipid phase. Nevertheless, these systems can be overwhelmed in times of increased oxidative stress, e.g. high metabolic demands or outside forces such as sunlight, smoking or pollution. This then results in oxidative damage of cell components, like proteins, lipids or DNA. Good examples for the consequences of repeated oxidative stress to skin are the aging process and aging‐associated skin cancers. There is much evidence that skin aging can be subdivided into intrinsic and extrinsic skin aging. Reactive oxygen species are not only involved in the metabolically induced intrinsic type of skin aging. Various exogenous sources of oxidative stress, in particular ultraviolet (UV)‐irradiation, are believed to be responsible for the extrinsic type of skin aging, therefore also termed photoaging. Regarding photocarcinogenesis, shorter wavelength UVB light is important for tumour initiation, but UVA light, which generates more oxidative stress, predominantly causes tumour promotion in nonmelanoma skin cancer. It therefore seems reasonable from various standpoints to increase levels of protective antioxidant systems. One feasible approach is to increase low‐molecular‐weight antioxidants through a diet rich in fruits and vegetables, systemic supplements or by direct topical application. Indeed, various in vitro and experimental animal studies have proved that dietary low‐molecular‐weight antioxidants or supplements, especially ascorbate and tocopherol as well as polyphenols and flavonoids, exert protective effects against oxidative stress. However, controlled long‐term studies on the efficacy of low‐molecular‐weight antioxidants in the prevention or treatment of skin aging in humans are still lacking.