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Burke. Plast Aesthet Res 2020;7:59 I http://dx.doi.org/10.20517/2347-9264.2020.154 Page 13 of 16

All environmental exposure - whether from solar energy or airborne toxins - leads to skin damage by
generation of ROS, either directly or via the AHR receptor. Our bodies’ primary protective mechanism is
our complex endogenous antioxidant network which is dependent upon external supplementation - either
orally, topically, or both. These antioxidant-induced reactions have been shown to combat extrinsic aging of
the skin and skin cancer. Indeed, the resident epidermal antioxidants vitamin C and vitamin E are depleted
55% and 25%, respectively, as they protect surface skin after exposure to high concentrations of O 3 [26] .

Antioxidants can best be replenished or delivered to the skin by topical application giving far higher
concentrations than attained by oral ingestion. For example, L-ascorbic acid (vitamin C) 15% gives 27-40 times
[66]
the skin concentration resulting from high oral intake , d-α-tocopherol 5% (the only one of 32 forms
[67]
of vitamin E that is effective on skin), by a factor of 12 , and selenium (L-selenomethionine 0.05%), by
a factor of 8 . These three antioxidants have been extensively studied and proven to prevent and even
[68]
[70]
reverse photoaging of the skin in mice [67,68,69] , pigs , and humans [71,72] , and to inhibit UV-induced skin
cancer in mice [67,68,69,73] . However, stringent criteria are required for topical formulations to be stable, to
[67]
[66]
be successfully absorbed, as to be active as antioxidants. Esterified forms of vitamins C and E are
not absorbed transcutaneously, and the ester is not reduced to the -OH form required for antioxidant
activity. Only the isomer d-α-tocopherol is effective; the other 31 isomers (eight “dl” isomer configurations
[67]
and four α, β, γ, δ forms) are not . High concentrations are required, optimally 15%-20% for l-ascorbic
[67]
[72]
acid and 2%-5% for d-α-tocopherol . Biologic L-selenomethionine is the optimal form of the multiple
[68]
valence forms of selenium (at concentrations of 0.02%-0.05%) . Combining L-ascorbic acid (15%) with
α-tocopherol (1%) gives four-fold protection against clinical minimal erythema dose (MED) and against
thiamine dimer formation alone ; addition of another plant antioxidant ferulic acid (0.5%) yields 8-fold
[74]
[72]
protection . This formulation was shown to prevent the up-regulation of oxidative and inflammatory
[75]
markers in human skin explants exposed to UV plus O and diesel engine exhaust . Many other topical
3
[76]
[77]
antioxidants are being actively studied, including lycopene , genistein , plant-derived phenolic
compounds (such as green tea, pomegranate, grape, and cocoa), and certain marine algae .
[78]
Current research is also focused on understanding at a cellular level how the AHR binds and metabolizes
xenochemicals, leading to complex cascades of protective or damaging inflammatory reactions, depending
upon the specific pollutant, simultaneous exposure to UVA and to other pollutants, and concentration of
these foreign substances. This understanding may lead to the discovery of methods to modulate the AHR
response in order to prevent and protect the skin from extrinsic damage.

DECLARATIONS
Acknowledgements
The author would like to thank Xueyan Zhou, MD, MS, for assistance with literature research and Heather
Nolan, MA, for excellent artistic rendition of the figures, literature research, and editing of text.

Authors’ contributions
The sole author wrote this review article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
The author declared that there are no conflicts of interest.