In Vitro Dermal Toxicity of Redox-Active Metal Nanocatalysts
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2019/03/01
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Description:Nanocatalysts (NCT) represent the convergence of catalysts, a mature technology with a new one, nanotechnology. NCT is a rapidly growing field that involves the use of nanomaterials as catalysts for a variety of catalytic applications. Since metal nanoparticles (MeNP) have a large surface-to-volume ratio compared to bulk materials, they are attractive candidates for use as catalysts. A number of redox-active MeNP and their oxides (MeO) including nickel (Ni) and cobalt (Co) are widely used. The physical nature and reactive surface properties of some of these may affect their ability to induce dermal toxicity thus causing adverse skin reactions. We hypothesize that toxicity of Me/MeO NP occurs via their ability to initiate oxidative stress, thereby inducing redox-sensitive transcription factors and triggering inflammation. Moreover, due to the skin's susceptibility to UV radiation, it is important to evaluate whether Me/MeO NP enhance the adverse effects of UVB. To test these hypotheses, the effects of Ni, Co, NiO, Co3O4 and CoO alone (0-26 microg/cm2) and co-exposed with UVB (4KJ/m2) were studied in vitro and in situ using murine epidermal cells (JB6 P+/+) and an engineered human skin construct (EpiDerm FT). Cell exposure to Me/MeO NP resulted in a dose- and time-dependent loss of cell viability, cell damage, oxidative stress and activation of AP-1/NF-kappaB. Co-exposure of Me/MeO NP with UVB ensued in amplification of the observed effects. Exposure of EpiDerm FT to Me/MeO NP caused tissue damage, oxidative stress and accumulation of inflammatory mediators. Hierarchical cluster analysis resulted in two major clusters separating cytokines production related to inflammatory cell recruitment (more intense) and TH2-type/regulatory immune responses (dimmed). UVB exposure alone induced significant tissue damage and secretion of cytokines/chemokines. Ni compounds drastically enhanced the post-UV treatment LDH release and secretion across the whole cytokine spectrum, while Co oxides prompted much weaker reaction. Interestingly, inflammatory cytokine/chemokine levels upon exposure to Me/MeO NPs, with or without UVB pre-treatment, followed similar trends compared to cell/tissue damage i.e., NiO>Ni>Co3O4>CoO and correlated with their size. Altogether, these results clearly indicate that some of the Me/MeO NP could induce cytotoxicity, oxidative stress and inflammation, and may potentially enhance response caused by UVB pre-treatment. [Description provided by NIOSH]
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ISSN:1096-6080
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Volume:168
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Issue:1
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NIOSHTIC Number:nn:20054994
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Citation:Toxicologist 2019 Mar; 168(1):285
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Federal Fiscal Year:2019
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Peer Reviewed:False
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Source Full Name:The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
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Main Document Checksum:urn:sha-512:5641d93a4179cade43af84a679f7fbacce27dd5b496c0ccff764514d2c5cd2433424a111b9ce5ea867c83b72d0b3bdd574ba579a69327dfb19925494fb2030c8
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