A Monocenter, Double-blind, Comparative, Controlled, Randomized Study to Evaluate the Effect of E212657 Compared to Placebo on Long UVA Induced Pigmentation in Healthy Volunteers.

The sun emits numerous radiations, of which 10% are constituted by ultraviolet light. Only ultraviolet B (UVB, 280-320 nm) and ultraviolet A (UVA, 320-400 nm) reach the surface of the earth. Poor penetrating UVB reach only to the deepest layers of the epidermis and cause DNA damage. UVA rays pass through the epidermis and reach the dermis due to their greater penetration property. UVA mainly generate intracellular oxidative stress. We can distinguish short UVA (320-340 nm) and long UVA (340-400 nm).

Sun exposure causes short-term consequences such as sunburn and reflects a reaction erythema, inflammatory type, and stimulation of pigmentation. One of the long-term deleterious consequences is represented by the development of skin cancers, which are the most dramatic result of sun exposure and are associated with mutations resulting from DNA damage badly repaired. The other long-term consequence is illustrated by the clinical signs of photoaging, associated with a major disruption in the dermal structure, linked both the decrease in collagen content and an increase in its degradation by some enzymes in the family of MMPs (matrix metalloproteinases). At the cellular and molecular level, many genes have their basal expression modulated in response to UV exposure (transcription factors and genes involved in DNA repair, inflammation, apoptosis, cell adhesion). Chronic sun exposure is also associated with the development or aggravation of pigmentary disorders, zones of hypo- or hyperpigmentation, actinic lentigo, melasma.

To protect ourselves from harmful effects of sun exposure, solar formulas applied to the skin, constitute a "barrier" against UV radiation. Currently, the most efficient sunscreen formulas from the market can absorb very efficiently and most of UVB and UVA rays. However, a part of long UVA (370-400nm) is not absorbed by these formulas, while these wavelengths seem to be involved in the generation of adverse biological effects on the skin, which may participate in clinical consequences of sun exposure, such as photo-aging and carcinogenesis. Biologically these wavelengths have been found to induce alteration at the tissue level, in particular the dermal layer, but also at the cellular and molecular levels, with for example the generation of oxidative stress and DNA damage.

Internal in vitro studies on skin cells in culture or on reconstructed skin showed that long UVA were the generators of oxidative stress, damage to DNA, cytotoxicity and modulation of genes or proteins involved in inflammation, the response to oxidative stress or photo-aging.

New sunscreens that are able to absorb beyond 370 nm, are now available. We have shown in an in vitro cultured cells or reconstructed skin that adding this type of filter in a state of the art formulation, allowed to shift the absorption spectrum beyond 370 nm and more. Thus it is possible to significantly reduce the biological impact of UVA long. These in vitro results strongly suggest a gain of biological protection by shifting the spectrum absorption beyond 370 nm.