SUN CARE
skin is exposed, coupled with the fact that they damage not only DNA but also its repair enzymes, the combined effects of pollution and other radiation wavelengths may now be quantitatively more important causes of skin cancer than UVB irradiation.
The role of antioxidants Although skin possesses numerous natural antioxidants to combat ROS, excessive or chronic exposure of tissues to oxidizing agents of any kind can overwhelm them. The most important natural antioxidants in skin are enzymes, such as glutathione peroxidase, superoxide dismutase, and catalase. Of secondary, but nevertheless significant,
importance are small endogenous and exogenous molecules, such as ubiquinol, uric acid, vitamin E, vitamin C, and carotenoids. There have been no controlled clinical trials of topical antioxidants for the prevention of skin cancer. Studies of the effects topical ascorbate,
alpha-tocopherol, retinyl palmitate, retinoic acid, and polyphenols on UV-induced ROS production, DNA lesions, and skin tumours in animals, and of topical ascorbate, vitamin E, and beta-carotene on UV-induced erythema in humans have recently been reviewed.64 Although the results were often encouraging,
depletion of the antioxidant was consistently observed during UV irradiation. Accordingly, the jury is out on whether more powerful synthetic antioxidants, such as the salen-manganese molecule EUK-13465, could significantly improve skin cancer prevention. More clinical data would be valuable.
A novel approach to counter lipid peroxidation ROS damage DNA and enzymes by both direct and indirect effects, the latter mediated by reactive aldehydes, such as the MDA and 4-HNE that are produced by their interactions with unsaturated fatty acids and other lipids in cell membranes and the interstitial fluid.66-68
A
novel approach to counter the effects of lipid peroxidation has been developed by Kutanios. Based on the knowledge that some of the
protein components of plasma lipoproteins have high binding affinities for lipid peroxides, the company has developed small peptides with similar physical properties for skincare. In cell culture, their lead peptide has been shown to almost completely protect the DNA of UV-irradiated keratinocytes from oxidative damage, and cell proteins from the formation of covalent adducts with 4-HNE.69
The approach
has several attractions. Peptides have a long history of safety in
skincare; if composed of L-amino acids, they are completely biodegradable; they pose no threats to the environment; they can be manufactured by green technologies; and the mechanism of action will apply to lipid peroxides produced by all ROS, what ever their origin. A further attraction is that lipid peroxides
have several other effects that promote the ageing of skin, increasing the secretion of matrix metalloproteinases and inflammatory cytokines, aggregating elastin, damaging collagen, and harming the lipid composition of the stratum
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IR AND VISIBLE
POLLUTION UVA ROS
Ozone NO2 PAHC Particles
LIPID PEROXIDES
MDA, 4HNE
DNA DAMAGE
UVB
Figure 3: Pathways by which solar radiation and atmospheric pollutants damage DNA. IR, infrared; VL, visible light; ROS, reactive oxygen species; MDA, malondialdehyde; 4HNE, 4-hydroxynonenal. ROS and lipid peroxides also damage DNA repair enzymes
corneum, important for maintaining the hydration of the skin.69 Being biodegradable, peptides of L-amino acids pose no threat to the environment, and can be manufactured by green technologies. A further attraction is sequestration of lipid peroxides is likely to be synergistic for DNA and enzyme protection with the protections afforded by radiation filters and antioxidants, and with the actions of matrikines for the general anti-ageing of skin.
Conclusion A striking feature of the field of skin cancer prevention is the contrast between the wealth of data from laboratory and experimental science and the paucity of data from clinical studies. Overall, the results suggest that UV screens
can be of benefit, especially if used from an early age, when applied correctly and regularly, and when users do not in consequence increase their exposure to sunlight in the mistaken belief that they are fully protected. Improvements in public education, to which the industry
can contribute, should help to counter these problems. Yet the likely reality is that no amount of
education will completely correct them, and that new technologies are needed. These could fall into three broad categories: filters that are less prone to photo-decompose, are without off-target activities, and absorb radiation over the entire UVA, UVB, and infra-red spectrum; antioxidants of greater potency and stability; and molecules that prevent or reverse the effects of ROS and their products, such as lipid peroxides, on DNA and enzymes. The last two categories have the additional
attraction of providing protection not only from sunlight, but also from the growing problem of atmospheric pollution. All new molecules should, of course, be biodegradable and without harmful effects on the environment. These are challenging objectives to which both industry and academia can contribute in tandem.
References to this article are available at:
https://bit.ly/3SXE9tp
April 2024 PERSONAL CARE
PC
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