دورية أكاديمية
Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage
| العنوان: | Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage |
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| المؤلفون: | Kahremany, Shirin, Babaev, Ilana, Gvirtz, Raanan, Ogen-Stern, Navit, Azoulay-Ginsburg, Salome, Senderowitz, Hanoch, Cohen, Guy, Gruzman, Arie |
| المصدر: | Skin Pharmacology and Physiology ; volume 32, issue 4, page 173-181 ; ISSN 1660-5527 1660-5535 |
| بيانات النشر: | S. Karger AG |
| سنة النشر: | 2019 |
| الوصف: | Background/Aims: The Nrf2 signaling pathway plays a pivotal role in neutralizing excess reactive oxygen species formation and therefore enhancing the endogenous cellular protection mechanism. Thus, activating this pathway may provide therapeutic options against oxidative stress-related disorders. We have recently applied a computer-aided drug design approach to the design and synthesis of novel Nrf2 enhancers. The current study was aimed at investigating the potential beneficial impact of (E)-5-oxo-1-(4-((2,4,6-trihydroxybenzylidene)amino)phenyl)pyrrolidine-3-carboxylic acid (SK-119) in skin oxidative damage models. Methods: SK-119, tested initially in PC-12 cells, attenuated oxidative stress-induced cytotoxicity concomitantly with Nrf2 activation. The potential impact of this compound was evaluated in skin-based disease models both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Results: The data clearly showed the marked anti-inflammatory and photoprotection properties of the compound; SK-119-treated cells or tissues displayed a reduction in cytokine secretion induced by lipopolysaccharides (LPS) in a manner comparable with dexamethasone. In addition, topical application of SK-119 was able to block UVB-induced oxidative stress and attenuated caspase-mediated apoptosis, DNA adduct formation, and the concomitant cellular damage. Conclusion: These results indicate that SK-119 is an Nrf2 activator that can be used as a prototype molecule for the development of novel treatments of dermatological disorders related to oxidative stress. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1159/000499432 |
| الإتاحة: | https://doi.org/10.1159/000499432Test https://www.karger.com/Article/Pdf/499432Test |
| حقوق: | https://www.karger.com/Services/SiteLicensesTest ; https://www.karger.com/Services/SiteLicensesTest |
| رقم الانضمام: | edsbas.48AC8CB3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1159/000499432 |
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