Vitamin C Compound Mixtures Prevent Ozone-Induced Oxidative Damage in Human Keratinocytes as Initial Assessment of Pollution Protection.
BACKGROUND
One of the main functions of cutaneous tissues is to protect our body from the outdoor insults. Ozone (O3) is among the most toxic stressors to which we are continuously exposed and because of its critical location, the skin is one of the most susceptible tissues to the oxidative damaging effect of O3. O3 is not able to penetrate the skin, and although it is not a radical per se, the damage is mainly a consequence of its ability to induce oxidative stress via the formation of lipid peroxidation products.


OBJECTIVE
In this study we investigated the protective effect of defined "antioxidant" mixtures against O3 induced oxidative stress damage in human keratinocytes and understand their underlying mechanism of action.


RESULTS
Results showed that the mixtures tested were able to protect human keratinocytes from O3-induced cytotoxicity, inhibition of cellular proliferation, decrease the formation of HNE protein adducts, ROS, and carbonyls levels. Furthermore, we have observed the decreased activation of the redox sensitive transcription factor NF-kB, which is involved in transcribing pro-inflammatory cytokines and therefore constitutes one of the main 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. In addition, a significant activation of Nrf2 in keratinocytes treated with the mixtures was also observed.


CONCLUSIONS
Overall this study was able to demonstrate a protective effect of the tested compounds versus O3-induced cell damage in human keratinocytes. Pre-treatment with the tested compounds significantly reduced the oxidative damage induced by O3 exposure and this protective effect was correlated to the abolishment of NF-kB nuclear translocation, as well as activation of Nrf2 nuclear translocation activating the downstream defence enzymes involved in cellular detoxification process.
Department of Life Science and Biotechnologies, University of Ferrara, Via L. Borsari, Ferrara, Italy; Department of Food and Function, Kyung Hee University, Seoul, South Korea.
Giuseppe
G
Valacchi
Department of Life Science and Biotechnologies, University of Ferrara, Via L. Borsari, Ferrara, Italy.
Claudia
C
Sticozzi
Department of Life Science and Biotechnologies, University of Ferrara, Via L. Borsari, Ferrara, Italy.
Giuseppe
G
Belmonte
Department of Life Science and Biotechnologies, University of Ferrara, Via L. Borsari, Ferrara, Italy.
Franco
F
Cervellati
L'Oreal Research & Innovation, Paris, France.
Julien
J
Demaude
L'Oreal Research and Innovation, Clark, New Jersey, United States of America.
Nannan
N
Chen
Skinceuticals, Inc., New York, New York, United States of America.
Yevgeniy
Y
Krol
L'Oreal Research and Innovation, Clark, New Jersey, United States of America.
Christian
C
Oresajo
D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D045022:Lactate Dehydrogenases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010126:Ozone / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D000975:Antioxidants; D016209:Interleukin-8; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D010126:Ozone; D045022:Lactate Dehydrogenases; D001205:Ascorbic Acid