where there is a high concentration of PM increases the risk of developing dark spots in the skin, wrinkles, and keratosis.7
Transition metals, primarily iron, and copper are a major component of PM derived from diesel exhaust. The redox potential of transition metals has for many years been explained by the Fenton reaction, in which hydrogen peroxide reacts with ferrous iron (Fe2+) to generate ferric iron (Fe3+) and hydroxyl radicals (HO•). The hydroxyl radical is one of the most harmful ROS due to its ability to react rapidly with lipids, inducing peroxidation and the formation of very reactive aldehydes, such as 4-hydroxy-nonenal (4HNE), which can then react with proteins and affect their physical properties.15
The harmful effects of PM may be amplified by UV exposure through a process called “photo-pollution.” In fact, in addition to the direct damage that UV light causes, it has also been shown to stimulate the release of cellular iron.16 If the accumulation of excess metals in skin tissue can be quenched, peroxidation and its harmful effects could be partially prevented.
Protection Against Environmental Stressors
Protecting the skin against all of these environmental pollutants is important if good dermatologic health is to be maintained. The skin plays a vital role as the first line of defense against pathogens and outdoor stressors in general, and it is well established that exposure to some solid particles in the atmosphere can bring about significant alterations to the skin.17 If the integrity of this barrier is damaged and compromised by environmental pollutants, it may become permeable to larger and even more harmful particles or microorganisms. Therefore, a more comprehensive approach to maintaining a healthy skin barrier should be a priority in today’s dermatology practice.
Although the skin is equipped with defense systems to counteract oxidative damage induced by environmental exposure, depletion of this system can also contribute to premature skin aging.18 Topical application of protective agents, including antioxidants, can help limit oxidative damage to skin tissue and reduce the subsequent inflammation that occurs. Ingredients of skin care preparations that can be helpful in this regard include vitamins A, C, and E; niacinamide (vitamin B); coenzyme Q; and caffeine.2,19,20 Natural plant extracts such as polyphenols, and especially flavonoids, have been increasingly used in recent years due to growing awareness of their antioxidant and anti-inflammatory properties.21,22
A newer approach to preventing skin damage caused specifically by transition metals present in PM is the use of chelating agents that can directly neutralize them. Chelating agents typically bind with metal ions in skin tissue to prevent them from participating in the Fenton reaction, and thereby attenuate the production of free radicals and ensuing lipid peroxidation that can occur due to accumulation of these metals.21
Several molecules are able to chelate iron, and a number have been studied for dermatologic use. Perhaps the most prominent example would be kojic acid, which is a natural metabolite produced by fungi. Kojic acid and its derivatives have a wide range of applications in health care and cosmetics, such as inclusion in some creams and lotions as a skin-lightening agent. They have also been shown to effectively bind excess iron and aluminum.23,24
Deferoxamine is a molecule produced by the bacterium Streptomyces pilosus that binds free plasma iron and excess iron inside cells with high affinity. It is, therefore, a highly potent iron chelator, and it has been administered systemically for more than 3 decades to treat acute or chronic iron overload. Once deferoxamine is bound to iron, it forms ferrioxamine, a highly water-soluble complex that is excreted by the kidneys.25 In addition to its ability to chelate transition metals, deferoxamine can also directly quench ROS, including HO• and superoxide (O2–), and it, therefore, has additional antioxidant properties.2
Iron-chelating activity has also been observed with some botanical agents, including baicalein and baicalin, flavonoids and other polyphenols, phytic acid, and chlorogenic acid.24,26-28 Some of these phytochemicals, such as flavonoids, also protect the skin by activation of the endogenous antioxidant system involving the transcription factor Nrf2, which is considered to be a crucial regulator of the innate cellular antioxidant defense.29
Metal Chelators in Skincare Products
The ability of chelating agents to protect the integrity of the skin has been examined in several scientific studies. Because iron-induced peroxidation contributes to the wrinkling that occurs as a result of chronic photodamage to the skin, topical administration of kojic acid was expected to have antiwrinkling activity. This theory was tested by exposing hairless mice to chronic UV radiation. After irradiation of the mice over a period of 20 weeks, mice that had been pretreated with topical kojic acid prior to UV irradiation were found to have much less wrinkling, hyperplasia of the epidermis, and fibrosis of the lower dermis, and an increase in extracellular matrix components in the upper dermis.30 In human skin, however, achieving adequate absorption of kojic acid has been a challenge and the use of novel delivery technology has been explored.31,32
