Redoxoma scientists led by Professor Maurício Baptista, from the Instituto de Química at the Universidade de São Paulo (USP), established the phototoxicity action spectrum of visible light in human keratinocytes. They showed that radiation in the violet and blue bands can have a toxic effect depending on the time of exposure to light, generating reactive species, damage to DNA, damage to mitochondria and lysosomes, and accumulating the pigment lipofuscin, which increases the cell sensitivity to visible light radiation. This is the first time that the effects of different ranges of visible light are compared in terms of phototoxicity on these cells. The study indicates that the available sunscreens, which protect against ultraviolet radiation (UVB and UVA), are insufficient for skin protection.

“Our article shows that high-energy blue, which we call violet here, should be an important target for the development of sunscreens. Violet is very close to 400 nanometers, which is the line that separates UVA from visible light. This line has no specific reason for the skin. It has a reason for our eyes, because we have receptors that see violet and blue and do not see UVA, and the skin does not have these receptors. However, in terms of wavelength and biological effect, these ranges are very similar to each other”, Baptista said. The results of the research, carried out during the doctorate of Paulo Newton Tonolli, the first author of the article, were published in the Journal of Photochemistry & Photobiology, B: Biology.

Unfortunately, according to the researchers, most people, including health professionals, remain unaware of the effects of visible light on the skin, and most companies that produce sunscreens ignore the fact that visible light penetrates deeper into the skin and induces redox imbalances and other cellular responses similar to those induced by UVA.

Sunbathing is healthy, but excess is harmful, warns Baptista, who is also studying the benefits of light for human health. Visible light exerts positive effects, such as tissue regeneration and pain relief, and even ultraviolet radiation has beneficial roles, such as the synthesis of vitamin D, for example. It is all a matter of dose.

The problem is that people feel protected by sunscreen and abuse sunbathing. With sunscreen, they can be protected against ultraviolet radiation but not against visible light. An indicator that something is not right is that, despite efforts for early detection and prevention of skin cancer, the prevalence of this cancer has been systematically increasing worldwide. The data appear in the article “The global burden of skin cancer: A longitudinal analysis from the Global Burden of Disease Study, 1990-2017”, published in the Journal of the American Academy of Dermatology (JAAD International) in 2021.

Toxic effects

Visible light comprises much of the energy of sunlight reaching the earth’s surface, covering the wavelength range from 400 to 750 nanometers. To investigate the differences between these visible light ranges, the researchers irradiated immortalized human skin keratinocytes (HaCaT) with physiologically relevant doses of the four main regions of visible light — violet, blue, green, and red.

They saw that the violet/blue component of visible light behaves similarly to UVA radiation in keratinocytes, producing DNA lesions. In addition, the violet/blue in the analyzed doses causes the malfunction of mitochondria and lysosomes, two key organelles for maintaining cell viability, inhibiting autophagic flux, and causing lipofuscin accumulation. Lipofuscin is an aggregate of oxidized biomolecules resulting from the incomplete digestion of cellular debris, that increases the cell sensitivity to visible light.

Visible light damages mitochondria and lysosomes, blocking the process of autophagy, and generating the accumulation of lipofuscin granules, which is a photosensitizer to visible light. In addition, photosensitization processes produce reactive oxygen species, which can damage nuclear and mitochondrial DNA (mtDNA). – Figure: M. Baptista et al.

In all experiments, violet light proved to be more toxic than blue, which, in turn, is more toxic than green. Only red light, at the dose used, did not cause significant damage to the studied biological targets. “This happens because more endogenous photosensitizers absorb in the violet than in blue and green, and almost none in red. These photosensitizers are the central key to everything”, explained Baptista.

Our skin is constantly hit by light. Billions of photons penetrate different layers of the skin, influencing its physiology. The damage mechanisms induced by solar radiation are mainly due to photosensitization, a process in which photosensitizers transform light energy into chemical reactivity. Photosensitizers are molecules that absorb photon energy and pass from the ground state to the excited state, which is more reactive.

UVB rays are the most deleterious for humans because they are absorbed by DNA and the photochemical effect is more direct. “DNA itself is the photosensitizer of UVB radiation.” In the case of visible light, photosensitization is indirect and depends on the various endogenous photosensitizers present in human skin, which absorb radiation and generate reactive oxidants. Photosensitizers are mainly vitamins, co-enzymes, and other co-factors, including, flavin, folic acid, nicotinamide, porphyrins and their derivatives, as well as, endogenous pigments such as melanin and lipofuscin. The susceptibility of cells, tissues, and organelles to damage caused by solar radiation depends on the presence and concentration of these endogenous photosensitizers. “Mitochondria and lysosomes, for example, have a large number of flavoproteins, and thus, of flavins”, says the researcher.

Visible light accounts for about 47% of the total solar radiation reaching human skin, compared to about 5% for UV radiation. And it is also the spectral range that forms the highest levels of free radicals generated in the skin under sun exposure, accounting for 50% of the total.

Partnerships

For several years and with numerous scientific contributions, Baptista has been warning of the need for new sun protection strategies that take into account the harmful effects of visible light.

Vice-coordinator of RIDC Redoxoma Technology Transfer, he is a consultant in Redoxoma’s partnerships with two companies interested in methods of detecting damage caused by visible radiation. One is Medcin Vitro, from the Medcin group, which, among other activities, tests the effectiveness of dermatological products and is developing tests to evaluate antioxidant effects and protection against visible light. “Two of the company’s partners are researchers associated with IQ-USP, and we have two agreements with FUSP”.

The international company Beiersdorf, owner of the brands Nívea, Coppertone, and Eucerin, is also in contact with the researcher to apply the tests described in this article on cells treated with a product developed to protect against visible light.

“Finally now we are -me and several others- managing to call the attention of companies that produce sunscreens”, said the researcher.

Meeting

Photochemistry and Photobiology scientists will gather at the meeting XV ELAFOT + 1^st LATASP, between October 23^rd and 26^th, in Maresias, São Paulo. The Encuentros Latinoamericanas de Fotoquímica y Fotobiología (ELAFOT) is a biannual meeting, held since 1982. LATASP is the Latin American Branch of the American Society for Photobiology, created in 2023, intending to unite Latin American researchers in Photobiology.

This edition of the event, organized by Baptista, will have more than 10 symposia, and the participation of scientists Jean Cadet, editor of Photochemistry and Photobiology, and Rex Tyrrell, editor of Photochemical & Photobiological Sciences (PPS), has already been confirmed.

The article The phototoxicity action spectra of visible light in HaCaT keratinocytes, by Paulo Newton Tonolli, Carlos M. Vera Palomino, Helena C. Junqueira and Mauricio S. Baptista, can be read here.