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SH-29 and SK-119 Attenuates Air-Pollution Induced Damage by Activating Nrf2 in HaCaT Cells

Author

Listed:
  • Shirin Kahremany

    (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel
    The Dead Sea and Arava Science Center, The Skin Research Institute, Masada 8691000, Israel)

  • Lukas Hofmann

    (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel)

  • Noy Eretz-Kdosha

    (The Dead Sea and Arava Science Center, The Skin Research Institute, Masada 8691000, Israel)

  • Eldad Silberstein

    (Department of Plastic Surgery, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 8410100, Israel)

  • Arie Gruzman

    (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel)

  • Guy Cohen

    (The Dead Sea and Arava Science Center, The Skin Research Institute, Masada 8691000, Israel
    Eilat Campus, Ben Gurion University of the Negev, Eilat 8855630, Israel)

Abstract

Air pollution has been repeatedly linked to numerous health-related disorders, including skin sensitization, oxidative imbalance, premature extrinsic aging, skin inflammation, and increased cancer prevalence. Nrf2 is a key player in the endogenous protective mechanism of the skin. We hypothesized that pharmacological activation of Nrf2 might reduce the deleterious action of diesel particulate matter (DPM), evaluated in HaCaT cells. SK-119, a recently synthesized pharmacological agent as well as 2,2′-((1E,1′E)-(1,4-phenylenebis(azaneylylidene))bis(methaneylylidene))bis(benzene-1,3,5-triol) (SH-29) were first evaluated in silico, suggesting a potent Nrf2 activation capacity that was validated in vitro. In addition, both compounds were able to attenuate key pathways underlying DPM damage, including cytosolic and mitochondrial reactive oxygen species (ROS) generation, tested by DC-FDA and MitoSOX fluorescent dye, respectively. This effect was independent of the low direct scavenging ability of the compounds. In addition, both SK-119 and SH-29 were able to reduce DPM-induced IL-8 hypersecretion in pharmacologically relevant concentrations. Lastly, the safety of both compounds was evaluated and demonstrated in the ex vivo human skin organ culture model. Collectively, these results suggest that Nrf2 activation by SK-119 and SH-29 can revert the deleterious action of air pollution.

Suggested Citation

  • Shirin Kahremany & Lukas Hofmann & Noy Eretz-Kdosha & Eldad Silberstein & Arie Gruzman & Guy Cohen, 2021. "SH-29 and SK-119 Attenuates Air-Pollution Induced Damage by Activating Nrf2 in HaCaT Cells," IJERPH, MDPI, vol. 18(23), pages 1-16, November.
    • Handle: RePEc:gam:jijerp:v:18:y:2021:i:23:p:12371-:d:687155
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    References listed on IDEAS

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    1. Qiao Li & Zhihua Kang & Shuo Jiang & Jinzhuo Zhao & Shuxian Yan & Feng Xu & Jinhua Xu, 2017. "Effects of Ambient Fine Particles PM 2.5 on Human HaCaT Cells," IJERPH, MDPI, vol. 14(1), pages 1-10, January.
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    4. Yang Ou & J. Jason West & Steven J. Smith & Christopher G. Nolte & Daniel H. Loughlin, 2020. "Air pollution control strategies directly limiting national health damages in the US," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
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