Iron oxide nanoparticles cause oxidative stress and dermal toxicity.
Murray-AR; Kisin-E; Inman-AO; Young-SH; Muhammed-M; Burks-T; Uheida-A; Tkach-A; Waltz-M; Castranova-V; Fadeel-B; Riviere-JE; Kagan-VE; Monteiro-Riviere-NA; Shvedova-AA
Toxicologist 2011 Mar; 120(Suppl 2):444
A number of commercially available metal/metal oxide nanoparticles (NP) such as superparamagnetic iron oxide (SPION) are utilized by the medical field for a variety of applications. We hypothesize that SPION may be toxic to skin via the ability of particles to be internalized and thereby initiate oxidative stress, inducing redox-sensitive transcription factors leading to inflammation. Due to the skin's susceptibility to UV radiation, it is also important to address the combined effect of UVB and NP co-exposure. To test this hypothesis, the effects of dextran-coated-SPION of different sizes (15-50 nm) and manufacturers (MicroMod (MM), Germany and Royal Institute of Technology, Sweden) were evaluated in 2 cell lines: human epidermal keratinocytes (HEK) and murine epidermal cells (JB6 P+). HEK cells exposed to 20 nm (KTH and MM) had a decrease in viability while the 15 and 50 nm particles were not cytotoxic. HEK cells were also capable of internalizing the KTH particles (15 and 20 nm) but not the MM SPION (20 and 50 nm). IL-8 and IL-6 were elevated in HEK cells following exposure to SPION. Exposure of JB6 P+ cells to all SPIONs evaluated resulted in activation of AP-1; however, only UVB plus SPION (15 and 20 nm KTH and 50 nm MM) resulted in significant NF-ęB induction in cells. Pre-exposure of JB6 P+ cells to UVB followed by NPs induced a significant depletion of glutathione, release of cytokines, and cell damage as assessed by release of lactate dehydrogenase. These data indicate that co-exposure to UVB and SPIONs was associated with induction of oxidative stress and release of inflammatory mediators. These results verify the need to thoroughly evaluate the adverse effects of UVB when evaluating dermal toxicity of engineered NPs on skin.
Biological-effects; Cell-biology; Cell-damage; Cell-function; Cellular-reactions; Cytotoxic-effects; Cytotoxicity; Cytotoxins; Immune-reaction; Immunotoxins; Molecular-biology; Molecular-structure; Nanotechnology; Oxidation; Oxidative-metabolism; Oxidative-processes; Particulate-dust; Particulates; Peroxidases; Physiological-effects; Quantitative-analysis; Quantitative-analysis; Skin-absorption; Skin-exposure; Skin-irritants; Skin-sensitivity; Statistical-analysis; Tissue-disorders; Toxic-effects; Toxic-materials; Toxicology; Toxins
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
University of Pittsburgh at Pittsburgh