التفاصيل البيبلوغرافية
| العنوان: |
Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage. |
| المؤلفون: |
Kahremany, Shirin, Babaev, Ilana, Gvirtz, Raanan, Ogen-Stern, Navit, Azoulay-Ginsburg, Salome, Senderowitz, Hanoch, Cohen, Guy, Gruzman, Arie |
| المصدر: |
Skin Pharmacology & Physiology; 2019, Vol. 32 Issue 4, p173-181, 9p |
| مصطلحات موضوعية: |
OXIDATIVE stress, PYRROLIDINE, CARBOXYLIC acids, LIPOPOLYSACCHARIDES, CYTOKINES |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
