Research Summary
One of the main functions of cutaneous tissues is to protect our body from outdoor insults. Ozone (O3) is among the most toxic stressors to which we are continuously exposed, and due to its critical location, the skin is one of the most susceptible tissues to the oxidative damaging effects of O3. While O3 is not able to penetrate the skin, and is not a radical per se, the damage is mainly a result of its ability to induce oxidative stress via the formation of lipid peroxidation products.
Aim of Study
In this study, we investigated the protective effect of defined "antioxidant" mixtures against O3-induced oxidative stress damage in human keratinocytes, aiming to understand their underlying mechanism of action.
Results
The results showed that the mixtures tested were able to protect human keratinocytes from O3-induced cytotoxicity and inhibited cellular proliferation. They also reduced the formation of HNE protein adducts, ROS, and carbonyl levels. Additionally, we observed a decrease in the activation of the redox-sensitive transcription factor NF-kB, which is involved in the transcription of pro-inflammatory cytokines and is one of the key players associated with O3-induced skin inflammation. Cells exposed to O3 demonstrated a dose-dependent increase in p65 subunit nuclear expression as a marker of NF-kB activation, while pre-treatment with the mixtures abolished NF-kB nuclear translocation.
Furthermore, significant activation of Nrf2 in keratinocytes treated with the mixtures was also observed.
Conclusion
Overall, this study demonstrated a protective effect of the tested compounds against O3-induced cell damage in human keratinocytes. Pre-treatment with these compounds significantly reduced oxidative damage induced by O3 exposure. This protective effect was correlated with the abolishment of NF-kB nuclear translocation and the activation of Nrf2 nuclear translocation, which activates downstream defense enzymes involved in the cellular detoxification process.
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