A Combination of Three Antioxidants Decreases the Impact of Rural Particulate Pollution in Normal Human Keratinocytes
Angelica Ortiz, Hong Sun, Thomas Kluz, Mary S. Matsui, Tiffany Carle, David Gan, Terry Gordon, Lucy Gildea, Max Costa- Colloid and Surface Chemistry
- Dermatology
- Drug Discovery
- Pharmaceutical Science
- Aging
- Chemistry (miscellaneous)
Abstract
Objective
It is well established that exposure of human skin to airborne pollution, particularly in the form of particulate matter sized 2.5 μm (PM2.5), is associated with oxidative stress, DNA damage and inflammation, leading to premature signs of skin aging. Because much of the damage results from oxidative stress, we examined the effects of a topical composition containing three antioxidants in an in vitro model system to assess the potential for amelioration of premature aging. The use of multiple antioxidants was of interest based on the typical composition of therapeutic skincare products. It is important to determine the efficacy of multiple antioxidants together and develop a short term assay for larger scale efficacy testing.
Methods
Normal human epidermal keratinocytes were exposed to a rural‐derived source of PM2.5 in the presence and absence of an antioxidant mixture of resveratrol, niacinamide and GHK peptide. Endpoints related to inflammation, premature aging and carcinogenicity were monitored after 5 hours of exposure and included IL‐6, CXCL10, MMP‐1, and NRF2. Differentially expressed genes were monitored by RNA‐seq.
Results
Pre‐treatment of keratinocytes with the antioxidant preparation in the absence of PM2.5 reduced baseline levels of MMP‐1, IL‐6 and CYP1A1 and reduced PM2.5 induced increases in all four endpoints, MMP‐1, IL‐6, CXCL10, and CYP1A1. Antioxidants significantly increased NRF2 protein in the presence of PM2.5, indicating a protective response. RNA‐seq interrogation of antioxidant treated cells further showed increased expression of NRF2 inducible genes. Expression of CYP1A1 and genes related to aryl hydrocarbon activation were induced by PM2.5 and suppressed by antioxidants.
Conclusions
Specific signaling pathways known to be correlated with skin inflammation and aging were examined based on their suitability for use in efficacy testing for the prevention of skin damage due to ambient hydrocarbon pollution. Endpoints examined after only 5 hours of exposure provide a useful method amenable to high through‐put screening. The results obtained reinforce the concept that a multiple antioxidant preparation, topically applied, may reduce pro‐inflammatory signaling and cellular damage and thereby reduce premature skin aging due to exposure to rural‐derived airborne pollution.