Involvement of 4-hydroxy-2-nonenal in pollution-induced skin damage

The effects of environmental insults on human health are a major global concern. Some of the most noxious pollutants that humans are exposed to include ozone (O 3 ), particulate matter (PM), and cigarette smoke (CS). Since the skin is the first line of defense against environmental insults, it is considered one of the main target organs for the harmful insults of air pollution. Thus, there is solid evidence that skin pathologies such as premature aging, atopic dermatitis (AD), and psoriasis are associated with pollutant exposure; all of these skin conditions are also associated with an altered redox status. Therefore, although the mechanisms of action and concentrations of O 3 , PM, and CS that we are exposed to differ, exposure to all of these pollutants is associated with the development of similar skin conditions due to the fact that all of these pollutants alter redox homeostasis, increasing reactive oxygen species production and oxidative stress. A main product of oxidative stress, induced by exposure to the aforementioned pollutants, is 4-hydroxy-2-nonenal (HNE), which derives from the oxidation of ω-6 polyunsaturated fatty acids. HNE is a highly reactive compound that can form adducts with cellular proteins and even DNA; it is also an efficient cell signaling molecule able to regulate mitogen-activated protein kinase pathways and the activity of redox-sensitive transcription factors such as Nrf2, AP1, and NFκB. Therefore, increased levels of HNE in the skin, in response to pollutants, likely accelerates skin aging and exacerbates existing skin inflammatory conditions; thus, targeting HNE formation could be an innovative cosmeceutical approach for topical applications.