Pereira AFC, Torloni LBO, Lage R, Cascais LC, Andrade CC, Yamashita JT, Moreira F, Clerici SP, Eberlin S, Pinheiro ALTA, Pinheiro AS.
The generation and activation of reactive oxygen species and other reactive agents can cause damage to cellular DNA and the immediate repair capacity of such damage is an important cellular mechanism that protects cells and maintains the genetic stability, preventing early oncogenesis. Mammalian cells have a defense mechanism designed to maintain genomic integrity and prevent the establishment of permanent damage resulting from genotoxic stress. In this context, the GADD45a protein (growth arrest DNA damage 45 alpha) plays a key role in cellular stress sensor through interaction with other proteins. In response to stress, GADD45a can promote the control of cell cycle regulation, DNA repair, epigenetic changes, apoptosis, survival and senescence. The purpose of this study was to evaluate the in vitro effectiveness of 18 sunscreens formulation in protecting against photodamage caused by ultraviolet radiation (UV) in cultured human fibroblasts. Our results showed that UV radiation produced a significant reduction of approximately 60% in the production of GADD45a when compared to non-irradiated control baseline (P<0.001). One possible explanation for this effect is the increase of consumption and degradation of this protein as a result of genotoxic stress, which could result in a transient reduction in the levels of GADD45a in fibroblast cultures. As mentioned, the absence of this protein can lead to genomic instability and the deficiency in the repair of DNA damage. On the other hand, concomitant incubation of cell cultures with photoprotective formulations prevented the marked reduction of this protein caused by UV radiation, promote up to 100% protection in the decrease of GADD45a. Extrinsic aging is attributed to changes in the skin due to lifestyle, being influenced mainly by ultraviolet radiation (UV), but also by pollution resulting from smoking, chemicals, heat and other environmental insults. One of the main targets of UV radiation is the DNA. The nitrogenous bases may undergo structural changes resulting in pyrimidine dimers that can destabilize the DNA molecule. In normal conditions of exposure, the body has enzyme systems that repair these changes in thymines, but cumulative and exposures for long periods, this system can fail and then, UV radiation trigger mutations in the DNA structure that can lead to the activation proto-oncogenes. The results presented in this work allow us to infer that cosmetic sunscreens have an important effect in the process of DNA damage repair generated as a result of genotoxic stress of UV radiation by reducing consumption and GADD45a degradation.