Vitamin C Compound Mixtures Prevent Ozone-Induced Oxidative Damage in Human Keratinocytes as Initial Assessment of Pollution Protection
Open accessAbstract
INTRODUCTION: 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. AIM OF STUDY: 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. CONCLUSION: 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Vitamin C mixtures prevented ozone-induced oxidative damage in human keratinocytes.
“In this regard, a recent study by Valacchi in 2015 showed that vitamin C mixtures prevented ozone-induced oxidative damage in human keratinoctyes [68].”
Application of antioxidant mixtures significantly reduced ozone-induced oxidative stress in human keratinocytes.
“A recent study showed that the application of antioxidant mixtures significantly reduced ozone-induced oxidative stress in human keratinocytes [37].”
From Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin (2017) · cites this paper as [37]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The relation between ozone, NOx and hydrocarbons in urban and polluted rural environments
Sillman, S. (1999) · Atmospheric Environment · doi:10.1016/s1352-2310(98)00345-8 · Cited by 1,800 · see citing works
Intrinsic and extrinsic factors in skin ageing: a review
Farage, M. A., Miller, K. W., Elsner, P., & Maibach, H. I. (2008) · International Journal of Cosmetic Science · doi:10.1111/j.1468-2494.2007.00415.x · Cited by 950 · see citing works
Oxidative stress and nuclear factor-κB activation
Bowie, A., & O'Neill, L. A. J. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00296-8 · Cited by 858 · see citing works
An Important Role of Nrf2-ARE Pathway in the Cellular Defense Mechanism
Lee, J., & Johnson, J. A. (2004) · BMB Reports · doi:10.5483/bmbrep.2004.37.2.139 · Cited by 746 · see citing works
Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin
Shindo, Y., Witt, E., Han, D., Epstein, W., & Packer, L. (1994) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12371744 · Cited by 546 · see citing works
Action of ascorbic acid as a scavenger of active and stable oxygen radicals
Niki, E. (1991) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/54.6.1119s · Cited by 489 · see citing works
Nrf2 Defends the Lung from Oxidative Stress
Cho, H., Reddy, S. P., & Kleeberger, S. R. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.76 · Cited by 463 · see citing works
Biochemical basis of ozone toxicity
Mustafa, M. G. (1990) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(90)90035-h · Cited by 386 · see citing works
Ferulic Acid Stabilizes a Solution of Vitamins C and E and Doubles its Photoprotection of Skin
Lin, F.-H., Lin, J.-Y., Gupta, R. D., Tournas, J. A., Burch, J. A., Angelica Selim, M., Monteiro-Riviere, N. A., Grichnik, J. M., Zielinski, J., & Pinnell, S. R. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23768.x · Cited by 365 · see citing works
Molecular Mechanism of Nrf2 Activation by Oxidative Stress
Kang, K. W., Lee, S. J., & Kim, S. G. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.1664 · Cited by 361 · see citing works
The cascade mechanism to explain ozone toxicity: The role of lipid ozonation products
Pryor, W. A., Squadrito, G. L., & Friedman, M. B. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(95)02033-7 · Cited by 340 · see citing works
Mechanisms of radical formation from reactions of ozone with target molecules in the lung
Pryor, W. A. (1994) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)90172-4 · Cited by 297 · see citing works
Cutaneous responses to environmental stressors
Valacchi, G., Sticozzi, C., Pecorelli, A., Cervellati, F., Cervellati, C., & Maioli, E. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06724.x · Cited by 243 · see citing works
Self-citationPaoletti, E., Marco, A. D., Beddows, D. C. S., Harrison, R. M., & Manning, W. J. (2014) · Environmental Pollution · doi:10.1016/j.envpol.2014.04.040 · Cited by 241 · see citing works
Environmental pollutants and skin cancer
Baudouin, C., Charvéron, M., Tarroux, R., & Gall, Y. (2002) · Cell Biology and Toxicology · doi:10.1023/a:1019540316060 · Cited by 232 · see citing works
Murray, J. C., Burch, J. A., Streilein, R. D., Iannacchione, M. A., Hall, R. P., & Pinnell, S. R. (2008) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2008.05.004 · Cited by 212 · see citing works
Aldehydes, hydrogen peroxide, and organic radicals as mediators of ozone toxicity
Pryor, W. A., & Church, D. F. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90186-7 · Cited by 170 · see citing works
Vitamins C and E donate single hydrogen atoms in vivo
Njus, D., & Kelley, P. M. (1991) · FEBS Letters · doi:10.1016/0014-5793(91)80672-p · Cited by 140 · see citing works
In vivo ozone exposure induces antioxidant/stress-related responses in murine lung and skin.
Valacchi, G., Pagnin, E., Corbacho, A., Olano, E., Davis, P., Packer, L., & Cross, C. (2004) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2003.12.005 · Cited by 139 · see citing works
Self-citationThiele, J. J., Traber, M. G., Tsang, K., Cross, C. E., & Packer, L. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00617-x · Cited by 138 · see citing works
Weber, S. U., Thiele, J. J., Packer, L., & Cross, C. E. (1999) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1999.00789.x · Cited by 125 · see citing works
Ozone exposure activates oxidative stress responses in murine skin
Valacchi, G., van der Vliet, A., Schock, B. C., Okamoto, T., Obermuller-Jevic, U., Cross, C. E., & Packer, L. (2002) · Toxicology · doi:10.1016/s0300-483x(02)00240-8 · Cited by 120 · see citing works
Self-citationNRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells
Pecorelli, A., Bocci, V. A., Acquaviva, A., Belmonte, G., Gardi, C., Virgili, F., Ciccoli, L., & Valacchi, G. (2012) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2012.12.001 · Cited by 117 · see citing works
Self-citationA new mechanism for the toxicity of ozone
Pryor, W. A., Squadrito, G. L., & Friedman, M. B. (1995) · Toxicology Letters · doi:10.1016/0378-4274(95)03563-x · Cited by 108 · see citing works
Ambient ozone pollution as a risk factor for skin disorders
Xu, F., Yan, S., Wu, M., Li, F., Xu, X., Song, W., Zhao, J., Xu, J. F., & Kan, H. (2011) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2011.10349.x · Cited by 104 · see citing works
Thiele, J. J., Podda, M., & Packer, L. (1997) · Biological Chemistry · doi:10.1515/bchm.1997.378.11.1299 · Cited by 87 · see citing works
Induction of stress proteins and MMP-9 by 0.8ppm of ozone in murine skin
Valacchi, G., Pagnin, E., Okamoto, T., Corbacho, A. M., Olano-Martin, E., Davis, P. A., van der Vliet, A., Packer, L., & Cross, C. E. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00812-x · Cited by 74 · see citing works
Self-citationUshio, H., Nohara, K., & Fujimaki, H. (1999) · Toxicology Letters · doi:10.1016/s0378-4274(98)00379-8 · Cited by 68 · see citing works
Effects of environmentally realistic levels of ozone on stratum corneum function
He, Q. C., Tavakkol, A., Wietecha, K., Begum‐Gafur, R., Ansari, S. A., & Polefka, T. (2006) · International Journal of Cosmetic Science · doi:10.1111/j.1467-2494.2006.00347.x · Cited by 63 · see citing works
Effects of atmospheric pollutants on the Nrf2 survival pathway
Rubio, V., Valverde, M., & Rojas, E. (2009) · Environmental Science and Pollution Research · doi:10.1007/s11356-009-0140-6 · Cited by 56 · see citing works
Antiproliferative effect of two novel COX-2 inhibitors on human keratinocytes
Sticozzi, C., Belmonte, G., Cervellati, F., et al. (2013) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2013.02.009 · Cited by 22 · see citing works
Self-citationCervellati, F., Pavan, B., Lunghi, L., Manni, E., Fabbri, E., Mascoli, C., Biondi, C., Patella, A., & Vesce, F. (2011) · Reproduction Fertility and Development · doi:10.1071/rd10077 · Cited by 16 · see citing works
Self-citationTroposphere ozone as a source of oxidative stress in cutaneous tissues
Sticozzi, C., & Valacchi, G. (2011) · Journal of Scientific & Industrial Research · Cited by 9 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 4
- [1]Health Effects Institute B, MA (2010) HEI Panel on the Health Effects of Traffic-Related Air Pollution. 2010. Traffic-Related Air Pollution: A Critical Review of the Literature on Emissions, Exposure, and Health Effects. HEI Special Report 17.
- [8]Thiele JJ, Podda M, Packer L (1997) Tropospheric ozone: An emerging environmental stress to skin. Biol Chem 378: 1299– 1305. 9426190
- [26]Pryor WA. (1994) Mechanisms of radical formation from reactions of ozone with target molecules in the lung. Free Radic Biol Med 17: 451– 65. 7835752
- [27]Thiele JJ, Traber MG, Tsang K, Cross CE, Packer L. (1997) In vivo exposure to ozone depletes vitamins C and E and induces lipid peroxidation in epidermal layers of murine skin. FRBM 23: 385– 391. 9214574
Cited by
Sorted by citations
Carr, A., & Maggini, S. (2017) · Nutrients · doi:10.3390/nu9111211 · Cited by 2,035 · see citing works
The Roles of Vitamin C in Skin Health.
Pullar, J., Carr, A., & Vissers, M. (2017) · Nutrients · doi:10.3390/nu9080866 · Cited by 756 · see citing works
Oxidative stress in the skin: Impact and related protection
Chen, J., Liu, Y., Zhao, Z., & Qiu, J. (2021) · International Journal of Cosmetic Science · doi:10.1111/ics.12728 · Cited by 351 · see citing works
Effects of air pollution on the skin: A review
Kathuria, S., Puri, P., Nandar, S., & Ramesh, V (2017) · Indian Journal of Dermatology, Venereology and Leprology · doi:10.4103/0378-6323.199579 · Cited by 282 · see citing works
Burke, K. E. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.12.003 · Cited by 136 · see citing works
Algae as an Attractive Source for Cosmetics to Counter Environmental Stress
Aslam, A., Bahadar, A., Liaquat, R., Saleem, M., Waqas, A., & Zwawi, M. (2021) · Science of The Total Environment · doi:10.1016/j.scitotenv.2020.144905 · Cited by 105 · see citing works
Environmental Air Pollutants Affecting Skin Functions with Systemic Implications
Bocheva, G., Slominski, R. M., & Slominski, A. T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310502 · Cited by 94 · see citing works
Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin
Naidoo, K., & Birch-Machin, M. (2017) · Cosmetics · doi:10.3390/cosmetics4010004 · Cited by 83 · see citing works
Keratinocytes oxidative damage mechanisms related to airbone particle matter exposure
Romani, A., Cervellati, C., Muresan, X. M., Belmonte, G., Pecorelli, A., Cervellati, F., Benedusi, M., Evelson, P., & Valacchi, G. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.11.007 · Cited by 52 · see citing works
Self-citationAir Pollution and Skin Diseases
Han, H. S., Seok, J., & Park, K. Y. (2025) · Annals of Dermatology · doi:10.5021/ad.24.159 · Cited by 28 · see citing works
- Authors
- Valacchi, G., Sticozzi, C., Belmonte, G., Cervellati, F., Demaude, J., Chen, N., Krol, Y., & Oresajo, C.
- Affiliations
- University of Ferrara (IT)
- L'Oréal (France) (FR)
- L'Oreal (United States) (US)
- Corresponding author
- Valacchi, Giuseppe
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-08-13
- Volume
- 10
- Issue
- 8
- Pages
- e0131097
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4536008
- OpenAlex
- W1125089188
- Cited by
- 90
- References
- 33
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 12 · 2020: 19 · 2019: 7 · 2018: 7 · 2017: 11 · 2016: 9 · 2015: 2
- FWCI
- 10.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- ozone, oxidative stress, human keratinocytes, antioxidant combination, vitamin C, lipid peroxidation, reactive oxygen species, carbonylation, NF-κB activation, Nrf2, skin inflammation, air pollution, skin protection, cytotoxicity
- MeSH terms
- Antioxidants, Ascorbic Acid, Cell Survival, Humans, Oxidation-Reduction, Ozone, Signal Transduction, Keratinocytes, Gene Expression, Interleukin-8, NF-kappa B, Reactive Oxygen Species, Oxidative Stress, Lactate Dehydrogenases, Cell Proliferation, NF-E2-Related Factor 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
