Physiologically relevant in vitro models to evaluate new compounds with skin protective effects against pollution and UV radiation

Abstract

The relationship between chronic and excessive sun exposure and photoaging and skin cancer is well established on the scientific literature. Furthermore, the relationship between environmental pollution and respiratory, cardiovascular and cancer diseases has also been widely studied. There are studies that indicate that some environmental pollutants absorb UV radiation and are considered to be photosensitizers, and high air levels of pollution can also be associated with inflammatory skin diseases. However, there are few studies in the literature that assess the possible effects of the combination between exposure to pollution and UV radiation in physiologically relevant models. There is also a lack of information related to the protection of UV-filters and antioxidants against this combination of solar radiation/environmental pollution, since some of these compounds are also described as photosensitizers. Thus, we propose to establish physiologically relevant in vitro models as a platform to explore new photostabilizers with protective effects against environmental pollution and UV radiation. For this, different exposure parameters to three different particulate matters of environmental pollution (PM 2.5 and PM 10, containing or not polycyclic aromatic hydrocarbons) and UV radiation in cell culture models in monolayers and in reconstituted human skin will be studied. The conditions of exposure of these models to particulate matters, by a nebulization system, aim to mimic the real conditions of exposure to pollution. Next, an evaluation of the most relevant markers for the assessment of exposure to the radiation/pollution/photounstable UV-filters system will be carried out, and the mechanism of protection and toxicity of this synergistic combination in a reconstituted human skin model will be studied. The inhibition of reactive oxygen species production, the gene expression of inflammatory mediators, enzymes and receptors altered by exposure to pollution and involved in the pathogenesis of skin diseases will be evaluated; in addition, the release of mediators in the culture medium will also be analyzed. Consequently, it will be possible to evaluate the photoprotective, antioxidant and photostabilizer potential of marine compounds, resveratrol and its analogues, obtained through partnerships in Brazil and abroad. It will also be possible to apply the developed model to evaluate new compounds that can protect the skin against damages induced by skin exposure to radiation/pollution/photounstable UV-filters. (AU)