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Effect of the flavonoids quercetin and taxifolin on UVA-induced damage to human primary skin keratinocytes and fibroblasts

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Abstract

The ultraviolet (UV) part of solar radiation can permanently affect skin tissue. UVA photons represent the most abundant UV component and stimulate the formation of intracellular reactive oxygen species (ROS), leading to oxidative damage to various biomolecules. Several plant-derived polyphenols are known as effective photoprotective agents. This study evaluated the potential of quercetin (QE) and its structurally related flavonoid taxifolin (TA) to reduce UVA-caused damage to human primary dermal fibroblasts (NHDF) and epidermal keratinocytes (NHEK) obtained from identical donors. Cells pre-treated with QE or TA (1 h) were then exposed to UVA light using a solar simulator. Both flavonoids effectively prevented oxidative damage, such as ROS generation, glutathione depletion, single-strand breaks formation and caspase-3 activation in NHDF. These protective effects were accompanied by stimulation of Nrf2 nuclear translocation, found in non-irradiated and irradiated NHDF and NHEK, and expression of antioxidant proteins, such as heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and catalase. For most parameters, QE was more potent than TA. On the other hand, TA demonstrated protection within the whole concentration range, while QE lost its protective ability at the highest concentration tested (75 μM), suggesting its pro-oxidative potential. In summary, QE and TA demonstrated UVA-protective properties in NHEK and NHDF obtained from identical donors. However, due to the in vitro phototoxic potential of QE, published elsewhere and discussed herein, further studies are needed to evaluate QE safety in dermatological application for humans as well as to confirm our results on human skin ex vivo and in clinical trials.

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Acknowledgements

We would like to express our thanks Iveta Hatalová (University Hospital Olomouc) for the support with skin tissue donor recruitment and Dr. Jana Franková (Department of Medical Chemistry and Biochemistry) for the extraction of human primary epidermal keratinocytes.

Funding

This study was financially supported by the grants IGA_LF_2021_011 and the Institutional Support of Palacký University, Olomouc—RVO 61989592.

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Authors and Affiliations

  1. Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 77515, Olomouc, Czech Republic

    Alena Rajnochová Svobodová, Alena Ryšavá, Lenka Roubalová, Jitka Ulrichová, Jiří Vrba & Jitka Vostálová

  2. Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 77900, Olomouc, Czech Republic

    Kateřina Čížková

  3. Department of Plastic and Aesthetic Surgery, University Hospital Olomouc, I. P. Pavlova 6, 77900, Olomouc, Czech Republic

    Bohumil Zálešák

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  1. Alena Rajnochová Svobodová
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Contributions

ARS and JVo designed the experiments, performed some experiments (ROS generation, GSH level, DNA damage) and wrote the first draft of the manuscript. AR was responsible for preparation of samples for immunocytochemical, Western blot and RT-PCR analysis. She also performed and evaluated Western blots. KC was responsible for the evaluation of immunocytochemical sections. LR and JVr were responsible for RT-PCR analysis. BZ was responsible for recruitment of skin tissue donors and sample collection. JU was responsible for critical proofreading of data and the text of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jitka Vostálová.

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The authors have no relevant financial or non-financial interests to disclose.

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The Ethics Committee of University Hospital Olomouc and the Faculty of Medicine and Dentistry, Palacký University, Olomouc approved the use of superfluous skin from human volunteers (ref. number 41/09). All volunteers signed their written informed consent.

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Rajnochová Svobodová, A., Ryšavá, A., Čížková, K. et al. Effect of the flavonoids quercetin and taxifolin on UVA-induced damage to human primary skin keratinocytes and fibroblasts. Photochem Photobiol Sci 21, 59–75 (2022). https://doi.org/10.1007/s43630-021-00140-9

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