Terrestrial organisms are chronically exposed not only to natural environmental stress factors, such as ultraviolet (UV) and ozone (O3
), but also to pollutants of anthropic origin. The skin, the largest body organ, provides the first barrier against environmental factors that physically and/or chemically can alter the body's functions. Indeed, the skin, along with the oral and respiratory tract, is the common route by which chemicals can enter the body.1
This protective envelope, fundamental for life on dry land and for animal evolution, consists of (a) the stratum corneum (corneocytes), which functions as a physical barrier against both percutaneous penetrations of harmful substances and excessive trans-epidermal water and salt loss; (b) a corneocytes-bound intercellular hydrophobic matrix, mainly composed of ceramides, fatty acids, and cholesterol, which forms a chemical barrier against the entry of environmental contaminants, including ambient particulate matters, as well as pathogens and allergens; and (c) an immunological barrier constituted by humoral and cellular components of the adaptive immune system, such as inflammatory cytokines and dendritic cells.
Alterations that disturb the skin barrier function in either stratum corneum lipid metabolism or protein components of the corneocytes are involved in the development of various less- or more-severe skin diseases, including erythema, edema, hyperplasia, “sunburn cell” formation, skin aging, contact dermatitis, atopic dermatitis, psoriasis, and carcinogenesis.2
Obviously, the protective ability of the skin is not unlimited, and problems arise when an abnormal exposure to environmental stressors exceeds the skin's normal defensive potential.
A major mechanism by which environmental insults exert a detrimental effect in the skin is through the generation of oxidative stress, which overwhelms the skin's defenses by quickly depleting the enzymatic (glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase) and nonenzymatic (vitamin E, vitamin C, and glutathione) antioxidant capacity, thus leading to deleterious effects.3
Sun UV rays, O3
, cigarette smoke (CS) exposure, and pollutants, in addition to the natural process of aging, contribute to the generation of free radicals and reactive oxygen species (ROS) that interact with lipid-rich plasma membrane and initiate the so-called lipid peroxidation reaction cascade
ROS also stimulate the release of pro-inflammatory mediators from a variety of skin cells. Skin inflammation, in turn, leads to skin infiltration by activated neutrophils and other phagocytic cells that generate further free radicals (both reactive oxygen and nitrogen species), thus establishing a vicious circle.7
Oxidative stress initiates complex biologic processes in various layers of the skin, which can result in transient or permanent genetic damage, activation of transcription factors, such as Ap1 and NF-κB,8
and signaling pathways, such as the ERK, JNK, and p38 MAPK pathways,9
involved in cell growth and differentiation and in degradation of the connective tissue of the dermis.10
Altered skin conditions are among the most common health problems in humans, even exceeding some of the most common pathologies such as obesity, hypertension, and cancer. More than 30% of the U.S. population has been affected by a skin disorder.11
And while many skin diseases are not life threatening or of sufficient societal concern and impact, they can have a significant clinical burden for individuals, affect quality of life, and account for substantial social health care costs.
The costs related to the main skin pathologies range from $157 million for cutaneous drug eruptions to $12.0 billion for skin ulcers and wounds; and the five most economically burdensome pathologies, based on direct and indirect costs, are skin ulcers and wounds, melanoma, acne, nonmelanoma skin cancer, and contact dermatitis, comprising a total of $22.8 billion in costs.12
Several environmental pollutants affect skin health and play a role in the pathogenesis of skin disease, among which UV, CS, and O3 have been shown to be the most dangerous, and thus will be discussed below.