Skin damage caused by wrong sunscreens: the photosensitization phenomenon
Prof. Luca Valgimigli
As we have seen in the previous article, many sunscreens get damaged by sun radiation as they absorb it. The modest photo-stability of such sunscreens has important consequences on the safety and efficacy of sun-care products based on them.
We have seen that photo-instability of sunscreens causes a reduction of sun protection factor (SPF) with time. There are, however, additional interactions of sunscreens with sunlight that have even worse consequences on their safety.
Solar radiation and the role of solar filters
Solar radiation contains sufficient energy to damage some molecules (M), including some molecules found in our skin, as exemplified in the equation:
M + light→ fragment-A + fragment-B
Fragments indicated as A and B, in the example above, are often free radicals that can attack other molecules, damaging or modifying them.
For instance, if such a reaction occurred in our skin, damage could occur to structural proteins like collagen and elastin, contributing to the formation of wrinkles and the onsetting of photo-aging. Furthermore, it could start chain-reactions leading to erythema, other inflammatory states and even genetic mutations (skin cancer).
Products containing sunscreens are meant to protect skin from all such damages, and normally they do, by decreasing the amount of UV radiation that hits our skin, i.e. acting as “filters”. CAUTION! Not all the sunscreens are friends of our skin, and actually some might cause bigger damage than that they are expected to prevent. How?
Let’s go back to our previous example. In order for M to react with light, it is necessary that molecule M is at least able to absorb the light at quantum level, i.e. it is necessary the energy carried by light photons hitting M corresponds exactly to the energy gap between quantum levels in the molecule. Often this is not the case and molecule M would be perfectly “safe” if it was not for the presence of other molecules called photosensitizers.
Benzophenone and main benzophenone derivatives used as sunscreen in sun-care cosmetic products as well as in the protection of manufacts. The common base structure is drawn in blue
F + light→ F*
F* + M → F + fragment-A + fragment-BT
This process is well known in photochemistry and benzophenone is among the photosensitizers of broader use in industrial processes to induce photochemical reactions. Benzophenone is also the lead structure for many and, unfortunately, very popular sunscreens, widely used in sun-care cosmetics to give sun protection factor. Most common examples are depicted in the figure above. Sunscreens like benzophenone-3 and benzophenone-4 are structurally related to benzophenone and are potent photosensitizers. In case M is a biomolecule in our skin, such as collagen, elastin, an enzyme or DNA, this can be damages by exposure to sunlight in the presence of photosensitizers (like benzophenone derivatives) much more it would happen in their absence. In other words, certain sunscreens can amplify the damage to our skin caused by sunlight.
For these reasons BeC does not use benzophenone derivatives in sun-care products!
BeC uses only physical filters in low protection products and, in high protection products, we use a combination of physical filters and new generation chemical filters, which are highly photostable. Here you can find more info on BeC sun-care products.
Therefore, when we chose a sun-care product, it is very important we pay attention to the label and read the composition: don’t look at the SPF value only!
We often hear that we should not expose to sunlight after having used perfumes or other products, as they can give photosensitization problems. The typical recommendation is to use only sunscreen products, but caution should be paid when we choose the sunscreen product, as even sunscreens can cause the same problems. Therefore, even if you have no particular problem of sensitivity to sunlight and think that any product will do the job, think again and don’t overlook the importance of choosing high quality sunscreens, so to make sure that the problems you don’t have will not be caused by the wrong product.
Many benzophenone derivatives are available today and 12 of them are of common use. Those more commonly used in the manufacture of sun-care cosmetics and other goods, are listed in the following.
- Benzofenone-1: 2,4-Dihydroxybenzophenone
- Benzofenone-2: 2,2′,4,4′-Tetrahydroxybenzophenone
- Benzofenone-3 (o oxybenzone): 2-Hydroxy-4-methoxybenzophenone
- Benzofenone-4 (o sulisbenzone): 2-Hydroxy-4-methoxy-benzophenone-5-sulphonic acid
- Benzofenone-5 (il sale sodico del sulisbenzone): Benzenesulfonic acid, 5-benzoyl-4-hydroxy-2-methoxy-, monosodium salt
- Benzofenone-8 (o dioxybenzone): 2-Hydroxy-4-methoxyphenyl)-(2-hydroxyphenyl)methanone
- Benzofenone-10 (o mexenone): 2-hydroxy-4-methoxy-4′-methyl-benzophenoneBenzofenone-11: it is a mixture of benzophenone 2 e 6.
Cyclooxygenase, lipoxygenase and the inflammatory process
Cyclooxygenase and lipooxygenase are the two families of enzymes that are commonly involved in the inflammatory process, through a complex of reactions which is called arachidonic acid cascade. This complex of reactions develops as follows: a first enzyme, a phospholipase cleaves the phospholipids of biological membranes, releasing arachidonic acid, a polyunsaturated fatty acid with 20 carbon atoms (eicosa-5Z,8Z,11Z,14Z-tetraenoic acid ; C20:4; ω-6). The arachidonic acid is then transformed by two parallel enzymatic pathways, that is, by two families of enzymes: the cyclooxygenase which transforms it into prostaglandins and thromboxanes and the lipooxygenase which transforms it into hydroperoxides which in turn transform into leukotrienes .
There are two cyclooxygenase isoforms indicated with type 1 and type 2, briefly COX-1 and COX-2. COX-1 is the enzyme present in most cells (except red blood cells), and is constitutive, that is, it is always present. COX-2 is an inducible cyclooxygenase isoform: it is constitutively present in some organs such as brain, liver, kidney, stomach, heart and vascular system, while it can be induced (i.e. developed if necessary) following inflammatory stimuli on the skin, white blood cells and muscles.
There are various types of lipooxygenase that lead to different products, the most important in the inflammatory process is 5-lipooxygenase, 5-LOX.
Prostaglandins, Thromboxanes, and Leukotrienes
Prostaglandins, Thromboxanes, and Leukotrienes are chemical messengers or mediators, that is, molecules that bring a message to specific cells and activate or deactivate metabolic responses in these cells. They, therefore, have a function similar to hormones, only that, unlike what hormones do, the chemical message is carried only at a short distance, that is, only to the cells that are in the vicinity of the place where the mediators were produced. There are different prostaglandins, different thromboxanes and different leukotrienes that carry specific messages. In many cases these act as mediators of the inflammatory process , therefore they trigger all the events that are involved in inflammation:
– vasodilation with consequent blood supply (redness),
– increased capillary permeability with consequent fluid exudation (swelling or edema),
– stimulation of nociceptive nerve signals (pain),
– on-site recall of immune system cells that attack a possible invader (chemotactic action)
– activation of the biosynthesis of fibrous tissue to strengthen or repair the affected part (even if there is no need)
– generations of free radicals that can chemically destroy an invader (but also damage our tissues, i.e. they just “shoot in the middle”).
Prostaglandins and thromboxanes, however, also play important physiological roles in normal conditions, i.e. in the absence of inflammation. For example, they regulate the secretion of mucus that protects the walls of the stomach, they regulate the biosynthesis of cartilages and synovial fluid in the joints, they regulate vasodilation, hence the correct flow of blood in the various local districts, and more.
Triglycerides are the main components of most oils and fats. These are heavy, non-volatile and little polar molecules, insoluble in water, made up of glycerol (or glycerin) esterified with three molecules of fatty acids: therefore, it is a tri-ester of glycerin, from which the name derives. Each fatty acid contains 8 to 22 carbon atoms (commonly 16 to 18) and can be saturated, mono-unsaturated or poly-unsaturated. The size of the fatty acids and their saturation determines the physical and sensorial properties of the triglycerides, which can appear as oils (liquids at room temperature) or fats (solid or semi-solid) and can have greater or less greasiness and smoothness on the skin. Unsaturated triglycerides or with shorter fatty acids are more fluid and have greater flowability.
Fatty acids (saturated, mono-unsaturated and poly-unsaturated)
The name fatty acids is commonly used to indicate those organic acids that are found in the composition of lipids, that is, in animal and vegetable oils and fats, both in the free form and in the form of esters with glycerol (e.g. in triglycerides), or they are esterified with “fatty” alcohols, that is, long chain alcohols, to form waxes. Fatty acids are carboxylic acids (formula R-COOH) which have a long carbon chain (R), unlike common organic acids such as acetic acid and propionic acid, which have 2 or 3 carbon atoms in total, respectively. Fatty acids are defined as saturatedif they do not have double carbon-carbon bonds, (called “unsaturations”), they are defined mono-unsaturated if they have only one, they are defined mono-unsaturatedpoly-unsaturated if they have two or more double bonds (see figure). The term omega-3 (ω-3) or omega-6 (ω-3), refers to the position of the first double bond starting from the bottom of the chain of carbon atoms: if the first double bond is encountered after 3 carbon atoms the fatty acid is classified as omega-3 , if after six carbon atoms omega-6 , as shown in the figure. The most common saturated fatty acids are palmitic acid (16 carbon atoms and no double bond, C16: 0) and stearic acid (18 carbon atoms, 18: 0), the most common mono-unsaturated is the oleic acid, typical of olive oil (18 carbon atoms and 1 double bond in position 9, C18: 1; ω-9), while the most common poly-unsaturated are linoleic acid and linolenic acid, progenitors respectively omega-6 and omega-3 (see figure).
Terpenes and terpenoids
Terpenes or terpenoids are a large family of natural molecules, typically containing 10 to 30 carbon atoms, which are biosynthesized from a common “brick”, isopentenyl pyrophosphate (IPP), containing 5 carbon atoms (see figure). The discovery that the repetitive brick consists of 5 carbon atoms is relatively recent, while it was once assumed that the entire family was created by repeating a brick of 10 carbon atoms, which was called “terpene”. Therefore, the molecules with 10 carbon atoms (such as limonene, see figure) were called mono-terpenes, i.e. composed of a single brick, diterpenes those with 20 carbon atoms (e.g. the cafestol that gives the aroma to the coffee), triterpenes those with 30 carbon atoms (e.g. beta-carotene). Since molecules made from 15 carbon atoms were also found (such as bisabolol), it was thought they contained a terpene and a half, and were called sesquiterpenes (from the Latin semis = half + atque = and). Today it is known that the repetitive unit is composed of 5 carbon atoms, therefore it is easy to understand how mono-terpenes contain two (see figure), sesquiterpenes three, diterpenes four, triterpenes six.