# Photoprotection

by Dr. Susana Encinas

Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain.

Reviewed by: Anonymous
Reviewed by: Anonymous
Date June 1st, 2018.

Photoprotection is the biochemical process that helps organisms cope with molecular damage caused by sunlight. Plants and other oxygenic phototrophs have developed a suite of photoprotective mechanisms to prevent photoinhibition and oxidative stress caused by excess or fluctuating light conditions. Humans and other animals have also developed photoprotective mechanisms to avoid ultraviolet (UV) photodamage to the skin, prevent deoxyribonucleic acid (DNA) damage, and minimize the downstream effects of oxidative stress.

Photoprotection of the human skin is achieved by extremely efficient internal conversion of DNA, proteins, and melanin. Internal conversion is a photochemical process that converts the energy of the UV photon into small, harmless amounts of heat. If the energy of the UV photon were not transformed into heat, then it would lead to the generation of free radicals or other harmful reactive chemical species (e.g. singlet oxygen, or hydroxyl radical).

Until recently, protection from sunlight has been limited to using sunscreens whose active ingredients are UV additives, which reflect or absorb UV rays depending on their chemical composition. Thus, the amount of radiation that penetrates the deeper skin layers is reduced and, consequently the effects of oxidative stress as burns, erythema, aging and cancer decrease. However, nowadays there is a growing interest in the use of additional ingredients in sunscreens for more protection. In addition, the principal damage triggered by the UV rays in a skin is caused by the generation of reactive oxygen species comprising free radicals.

In this context, the skin possesses a wide range of interlinked antioxidant defence mechanisms to protect itself from damage by UV-induced reactive species. However, the capacity of these systems is limited, and they can be overwhelmed by large doses of UV and especially chronic UV exposure. This offers interesting opportunities for enhancing and/or supporting these endogenous defence mechanisms to improve UV protection in the skin.

## 1 Ultraviolet Incidence on Earth

UV light has played an essential role in the development and evolution of the life bricks and the current life forms on Earth. It is well known that the amount of incident UV radiation has important implications for human health and terrestrial and aquatic ecosystems. Nevertheless, concern about the harmful effects of over-exposure to sunlight has been growing for quite some time. The negative effects, which range from non-melanoma skin cancer (by far the most prevalent cancer in the world) and premature skin ageing to immunosuppression, were found to be specifically linked to the UV-part of the solar spectrum.

Only a small fraction of the radiation emitted by the sun that reaches the earth’s surface resides in the UV range. This corresponds to less than 6% (amount that varies according to the ozone layer, clouds, air pollution, etc. in each place) of the solar electromagnetic spectrum. The UV wavelength range extends from 100 to 400 nm, and it is divided into UVC (100–280 nm), UVB (280–315 nm), and UVA (315–400 nm). UVA is further divided into UVA1 (340-400 nm) and UVA2 (315-340 nm).The shorter the wavelengths, the greater the absorption by the atmosphere, the most energetic UV photons belonging to vacuum UV radiation. Ozone and oxygen completely absorb UVC radiation and absorb the majority (approximately 90%) of UVB. Therefore, UVA accounts for approximately 95% of the total UV energy that reaches the Earth’s surface, with the remaining 5% being UVB.

UVB light is photobiologically very active, even though it represents only a small part of the total intensity of the solar light that reaches the earth’s surface. The exposure to UV radiation is increasing due mainly to changes in lifestyle (more outdoor activities), and as a result of the reduced ozone levels in the stratosphere.[1]

## 2 Biomolecule Damage Induced by UVB and UVA: Photoinduced DNA Damage

The understanding of UV radiation (UVR) and its effects on the skin is constantly evolving. UV can cause damage directly, when the light is absorbed by essential biomolecules (DNA, proteins or lipids), but also indirectly, by inducing reactive intermediates in the skin. These reactive species usually are reactive oxygen species (ROS), such as H$_{2}$O$_{2}$, superoxide anion, hydroxyl radical and singlet molecular oxygen. The induction of ROS by UV can occur directly or through (endogenous) photosensitized reactions (see Photosensitization entry[[1]]). Although ROS normally have a short half-life, they can react with other compounds in the skin including DNA, proteins and lipids.This results in DNA strand breaks and oxidative damage, protein-protein and protein-DNA crosslinks and oxidative lipid damage. Therefore, ROS are thought to be an important cause of skin cancer and premature skin aging. [2,3]

The UV spectrum has an effect on the skin aging, sunburn development, the production of precancerous and cancerous lesions, and immunosuppression. The incidence of skin cancer in humans has increased considerably in recent decades. Exposure to solar ultraviolet radiation is certainly involved in numerous skin pathologies. In this context, the role of sunlight UV radiation as an initiator of cancer and as a promoter of cancer is no longer in question.[4]

The mechanisms involved in the UV damage of biomolecules are largely based on the direct absorption of light to form more reactive, electronically excited molecules. Although UVR represents only a small part of the solar spectrum, it has enormous importance on the structure of the atmosphere, and it has a critical impact on the biosphere. In this regard, the main biological effect of UV radiation resides in the formation of DNA damage in diﬀerent aquatic and terrestrial life forms. Because the maximum light absorption by DNA molecule is observed at 260 nm, UVC would be the most eﬀective waveband for the induction of DNA photoproducts; however, these short wavelengths are entirely blocked by the earth’s atmosphere. Nevertheless, the energy of incident UVB and UVA photons is high enough to generate DNA damage, being UVA capable of penetrating the skin more eﬃciently than UVB, reaching the basal layers where melanocytes and dividing stem cells are located.[5]

Figure 1. Sunlight-DNA interactions and effects.

The mechanisms of damage differ for UVB and UVA radiation.[6,7] UVB is still absorbed directly by the DNA so that this sunlight component is considered the most mutagenic and carcinogenic. Although UVA radiation is at least ten times more abundant than UVB in the solar spectrum, it doesn’t cause directly damage to DNA but may act through photosensitized reactions due to endogenous or exogenous chromophores contained in several compounds as drugs, cosmetics, etc.(see Photosensitization entry [[2]]). This photosensitizing DNA damage by xenobiotics has attracted considerable attention because it can involve a more extended active fraction of the solar spectrum with carcinogenic potential, as it is shown in Figure 1. In that way, the risk of damage to biomolecules is considerably increased.[8]

To sum up, UVB typically induces erythema, acute sunburn and direct DNA damage via pyrimidine dimer formation, whereas UVA is mainly associated with generation of reactive oxygen species (ROS) contributing to photoaging and photocarcinogenesis. Therefore, DNA damage is considered to be the main cause for the genetic changes responsible for sunlight-induced skin lesions and carcinogenesis, including malignant melanoma.[5]

## 3 Sunscreens and Photoprotection

The need for photoprotection today is more apparent than ever, with a 20% incidence of non-melanoma skin cancer in humans during their lifetime, the majority of these cancers attributable to a lifetime of cumulative UV radiation exposure. The ability for individuals to practice photoprotection is becoming more facile as newer sunscreen agents and technology block UVR more effectively.[4]

As part of a strategy of photoprotection against cell damage is necessary to consider the implementation of several consecutive lines of defence. Among them the development of sunscreens to minimize light absorption by the photosensitizers and the use of scavengers to eliminate the reactive oxygen species arising therefrom.On the other hand, the skin contains an interlinked system of antioxidants. These antioxidants, which include not only glutathione, ascorbate and $\alpha$-tocopherol but also enzymes, are usually sufficient to deal with UV-induced oxidative stress. However, excessive exposure to UV reduces the levels of the antioxidants in the skin, allowing the ROS to reach damaging levels.[9] Therefore a more comprehensive strategy for photoprotection could include the use of antioxidants.

There are three principal ways to protect the skin against the UV rays: reflect the rays away from the skin; absorb the rays and deactivate them; prevent and repair the damage they cause. The ideal sunscreen should therefore contain chemicals that address all three. Indeed, sunscreens may contain agents, which mainly would reflect UV rays, and/or photo-stable UV absorbers, which would absorb the rays in different ways according to their chemical structure in order to provide broad-spectrum coverage (see Photostable Compounds entry [[3]]). The third issue may be addressed by using free radical scavengers/antioxidants and agents active in DNA repair to improve photoprotection.[10]

### 3.1 Active Sunscreen Ingredients: UV Filters

Sunscreens are used to protect human skin against harmful UV radiation. They are first-line protection from UVR and its negative effects, as it is schematized in Figure 2. Therefore, the purpose of UV filters used in cosmetic sunscreen formulations is to attenuate the UV radiation of the sun minimizing the extent of UVB and UVA radiation that might reach DNA in the cell nuclei. [11] In this regard, sunscreens are widely proved to decrease the signs of photoaging and the incidence of skin cancers.Thus, because UV radiation is the major cause of the clinical changes in skin exposed to sunlight, it is extremely important to accurately assess the photoprotection properties of sunscreens in order to prevent harmful consequences caused by prolonged sun exposure, especially for hypersensitive individuals.[4]

Figure 2. Photoprotection strategy: UV-filtering effect.

Sunscreens have been available since 1928 and today play a major role in skin cancer prevention and sun protection. Their use as an integral part of the photoprotection strategy has been expanded worldwide. Their active ingredients are generally divided into inorganic and organic agents, previously termed physical blockers and chemical absorbers, respectively. On the one hand, inorganic sunscreen ingredients act by reflecting or scattering visible, UV, and infrared radiation over a broad spectrum. The major inorganic agents used today are zinc oxide and titanium dioxide. On the other hand, organic sunscreen ingredients, many of which specifically filter UVB, act by absorbing UVR and converting it into heat.[12]

In this context, the fundamental component of a good sunscreen is a broad-spectrum (UVA/UVB) coverage, absorbing over the entire UV spectrum, because of UVA- and UVB-blocking products protect against sunburn as well as subtler suberythemal skin damage. Only in that way a sunscreen would be able to prevent or significantly reduce the photoinduced biological damage.[13]

#### 3.1.1 Principles of UV Radiation Absorption by Organic UV Filters

The principle of photoprotection in organic sunscreens is the absorption of UVR. In order to absorb the UVR an organic UV light ﬁlter must contain a suitable chromophore having conjugated $\pi$-electron systems. Increasing the number of conjugated double bonds in the molecule, the absorption maximum shifts to longer wavelengths and also gives rise to a larger absorption cross section and, therefore, stronger absorption. In general, the higher the molecular weight of the chromophore, the larger the absorption maximum shifts towards longer wavelengths. This is the reason why UVB ﬁlters have smaller molecular weights compared to UVA or broad spectrum ﬁlters.

Currently, all organic UV absorbers used in sunscreens are aromatic compounds, each containing multiple conjugated $\pi$-electron systems. Furthermore, also the type of substituents and their position on the aromatic ring are important for the UV absorption properties. Especially advantageous are disubstituted systems with an electron-donor and an electron-acceptor group in thepara position (so-called push-pull systems).

Figure 3. Top: Chemical structures of three solar filters. Bottom: UV-Vis absorption spectra of the filter molecules with different UV coverage.

Sunscreens, which mainly absorb UVB, may be less effective in preventing UV radiation-induced immunosuppression than broad-spectrum products. [14] Absorption of an UV photon brings the organic UV absorber into an excited electronic state, either a singlet (short lived) or a triplet (longer lived) one. The excited molecule may reach an equilibrium through reversible isomerization or, under certain conditions, return to its original form (ground state). The energy of the excited electronic state may dissipate after internal conversion into molecular vibrations and further into heat via collisions with surroundings molecules, or have a radiative deactivation (fluorescence from the singlet state or phosphorescence from the triplet state).[15]

In this context, one approach to enhancing sunscreens is to develop innovative UV filters that are suitable and safe for human use. Most sunscreen agents provide protection in a particular UV range and offer insufficient photoprotection when used alone. In this sense, two factors must be addressed to produce an “ideal” sunscreen. First, it should provide uniform protection across the range of UVB and UVA, which assures that the natural spectrum of sunlight, is attenuated in a uniform manner. Then, broad-spectrum (UVB/UVA) products are produced by combining filters with varying UV absorption spectra (see Figure 3). In the second place, the “ideal” sunscreen should also have pleasing sensory and tactile profiles that enhance the user’s acceptance.[16]

Furthermore, considering the photoprotective strategy described above (Figure 2), sunscreen formulations including species with triplet quenching ability could provide effective protection from the potential phototoxic and photoallergic effects derived from poor photostability of some filters. [17] As an example, BEMT (whose chemical structure is described in Figure 3) is reported as a highly photostable filter that may also act as a triplet quencher because it is able to deactivate photolabile UV absorbers through triplet-triplet energy transfer. Then, this triplet quencher returns to its ground state dissipating the accepted energy (see Photostable Compounds entry [[4]]). In this regard, being aware of these mechanisms and applying them for specific UV filter combinations can help in designing efficient sunscreens.

### 3.2 Antioxidants

At present, there is a trend toward a higher sun protection factor (SPF) and extra ingredients are included in the formulation of sunscreens to achieve further protection against the indirect damage primarily caused by the deeper penetrating UVA rays. In fact, supporting the cutaneous antioxidant defence system is one of the most promising strategies for providing photoprotection. In that context, vitamins, plant extracts and synthetic antioxidants are being incorporated in sunscreens as an additional measure to delay the aging process and reduce the skin photodamage induced by an excessive exposure to solar radiation.[12]

Moreover, the use of antioxidants is reinforced by recent results showing that solar filters can promote DNA damage. [17,18] Actually, topical antioxidants and DNA repair stimulants are being explored as options for expanding the photoprotective abilities of sunscreens, as shown in Figure 4. In this context, these additives have been incorporated into many sunscreen formulations to neutralize the cytotoxic effects of ROS generated by UV exposure.[19]

Figure 4. Photoprotection strategy: Antioxidant ability.

In this regard, compounds with antioxidant ability would have the potential of adding protection against the effects of UV radiation. However, a 2011 study concluded that all tested sunscreens had minimal or no antioxidant properties, most likely because of the lack of stability of the antioxidant compounds. [16] Thus, a variety of new supplements were studied recently in order to improve photoprotection. Among these compounds, flavonoids, resveratrol and green tea extracts are reported to probably diminish UV-related skin damage, although they can be unstable and diffuse poorly into the epidermis. Such antioxidants are inefficient UV filters and have low SPF; therefore, they are commonly used in combination with sunscreens to enhance their efficacy. [20] In fact, several studies have shown that a combination of UV absorbers plus antioxidants is more effective in protecting skin against sun over-exposure than UV absorbers or antioxidants alone.[10]

In conclusion, recommended photoprotective measures include sun avoidance during the peak UVR (10 AM-4 PM), the use of photoprotective clothing, wide-brimmed hat, sunglasses, and the use of broad-spectrum sunscreens. There are many other agents with photoprotective properties, which range from antioxidants to plant extracts to DNA repair enzymes. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. Continued investigations in this area should result in the development of even more effective photoprotective agents in the future.

## 4 References

[1] McKenzie, R. L.; Aucamp, P. J.; Bais, A. F.; Bjorn, L. O.; Ilyas, M.; Madronich, S. (2011) Ozone depletion and climate change: impacts on UV radiation.Photochem. Photobiol. Sci. 10:182-198.

[2] Miyachi, Y. (1987) The biological roles of reactive oxygen species in skin.Reactive oxygen species in photodermatology. O. Hayaishi, S. Imamura and Y. Miyachi, Eds., University Press: Tokio, 37-41.

[3] Miyachi, Y. (1995) Photoaging from an oxidative standpoint.J. Dermatol. Sci. 9: 79-86.

[4] Palm, M. D.; O’Donoghue, M. N. (2007) Update on photoprotection. Dermatologic Therapy 20:360-376.

[5] Passaglia Schuch, A.; Machado Garcia, C. C.; Makita, K.; Martins Menck, C. F. (2013) DNA damage as a biological sensor for environmental sunlight. Photochem. Photobiol. Sci.12:1259-1272.

[6] Cadet, J.; Mouret, S.; Ravanat, J. L.; Douki, T. (2012) Photoinduced damage to cellular DNA: direct and photosensitized reactions. Photochem. Photobiol. 88:1048-1065.

[7] Sage, E.; Girard, P. M.; Francesconi, S. (2012) Unravelling UVA-induced mutagenesis. Photochem. Photobiol. Sci. 11:74–80.

[8] Miranda, M. A. (2001) Photosensitization by drugs. Pure Appl. Chem. 73:481-486.

[9] Steenvoorden, D. P. T.; Beijersbergen van Henegouwen, G. M. J. (1997) The use of endogenous antioxidants to improve photoprotection. J. Photochem. Photobiol. B:Biol. 41:1-10.

[10] Damiani, E.; Astolfi, P.; Greci, L. (2008) Nitroxide-based UV-filters: a new strategy against UV-damage? Household and Personal Care Today 2:20-23.

[11] Herzog, B.; Wehrle, M.; Quass, K. (2009) Photostability of UV absorber systems in sunscreens. Photochem. Photobiol. 85:869-878.

[12] Sambandan, D. R.; Ratner, D. (2011) Sunscreens: An overview and update. J. Am. Acad. Dermatol. 64:748-758.

[13] Fourtanier, A.; Moyal, D.; Seite, S. (2012) UVA filters in sun-protection products: regulatory and biological aspects. Photochem. Photobiol. Sci. 11:81-89.

[14] Moyal, D. D.; Fourtanier, A. M. (2008) Broad-spectrum sunscreens provide better protection from solar ultraviolet-simulated radiation and natural sunlight-induced immunosuppression in human beings. J. Am. Acad. Dermatol. 58:149-154.

[15] Chatelain, E.; Gabard, B. (2001) Photostabilization of butyl methoxydibenzoylmethane (Avobenzone) and ethylhexyl methoxycinnamate by bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), a new UV broadband filter. Photochem. Photobiol. 74:401-406.

[16] Jansen, R.; Osterwalder, U.; Wang, S. Q.; Burnett, M.; Lim, H. W. (2013) Photoprotection Part II. Sunscreen: Development, efficacy and controversies. J. Am. Acad. Dermatol. 69:1-14.

[17] Paris, C.; Lhiaubet-Vallet, V.; Jimenez, O.; Trullas, C.; Miranda, M. A. (2009) A blocked diketo form of avobenzone: Photostability, photosensitizing properties and triplet quenching by a triazine-derived UVB-filter. Photochem. Photobiol. 85:178-184.

[18] Bastien, N.; Millau, J. F.; Rouabhia, M.; Davies, R. J. H.; Drouin, R. (2010) The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid photosensitizes the formation of oxidized guanines in cellulo after UV-A or UV-B exposure. J. Invest. Dermatol. 130:2463-2471.

[19] Afonso, S.; Horita, K.; Sousa e Silva, J. P.; Almeida, I. F.; Amaral, M. H.; Lobao, P. A.; Costa, P. C.; Miranda, M. S.; Esteves da Silva, J. C. G.; Sousa Lobo, J. M. (2014) Photodegradation of avobenzone: Stabilization effect of antioxidants. J. Photochem. Photobiol. B:Biol. 140:36-40.

[20] Kullavanijaya, P.; Lim, H. W. (2005) Photoprotection. J. Am. Acad. Dermatol. 52:937-958.