Comparative toxic effects of nickel oxide nanoparticles in skin.
Murray-AR; Kisin-E; Tkach-A; Young-SH; Castranova-V; Fadeel-B; Kagan-VE; Shvedova-AA
Toxicologist 2012 Mar; 126(Suppl 1):299-300
Nickel (Ni) and nickel oxide (NiO) nanoparticles (NPs) are already commercially available and utilized by the medical and chemical industries for a number of pharmaceutical and engineering applications. The physical nature of NPs and their reactive surface properties may affect their ability to induce dermal toxicity thus causing adverse skin reactions. Although Ni is widely known to cause a number of skin ailments, e.g. hypersensitivity, contact dermatitis and skin cancer, the effects of nanosized Ni/NiO NP in comparison to particles of larger size are unknown. We hypothesize that Ni NPs are more toxic to the skin than larger Ni particles and this toxicity occurs via the metal's ability to initiate oxidative stress, thereby inducing redox-sensitive transcription factors thus affecting/leading to inflammation. Because of the skin's susceptibility to UV radiation, it is also important to evaluate the combined effect of UV-B and Ni/NiO NP co-exposures. To test the hypothesis, the effects of Ni/NiO particles were studied using murine epidermal cells (JB6 P+) and BALB/C mice. In vitro, Ni/NiO particles resulted in activation of AP-1 and NF-kappaB as well as the induction of hypoxia inducible factor-1alpha (HIF-1alpha) which is involved in upregulating MMP-2 and MMP-9. Additionally, co-exposure of JB6 P+ cells to UVB and Ni/NiO particles resulted in significantly accelerated cell damage and death, accumulation of oxidative stress markers (4-HNE and protein carbonyls), antioxidant decrease (GSH), and release of pro-inflammatory cytokines. In vivo, the ability of Ni/NiO to induce contact hypersensitivity was evaluated. Exposure to nanosized particles induced greater sensitization than was observed from larger Ni/NiO PM. Altogether, these data indicate that co-exposure of dermal cells in vitro to UVB and Ni/NiO NPs was associated with greater induction of oxidative stress, antioxidant depletion and release of HIF-1alpha and inflammatory mediators as compared to those treated with NP alone.
Nanotechnology; Health-hazards; Immune-system; Immune-reaction; Cell-function; Cellular-reactions; Molecular-biology; Laboratory-testing; Laboratory-animals; Cytotoxic-effects; Cell-damage; In-vitro-study; Surface-properties; Skin-exposure; Skin-irritants; Skin-sensitivity; Dermatology; Toxic-effects; Toxic-materials; Oxidative-processes; Oxidation-reduction-reactions; Ultraviolet-radiation; Antioxidants
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California