nanoparticles; translocation; inhalation; superparamagnetic iron oxide nanoparticles-SPIONs; tobacco smoke nanoparticles; exhaled breath condensate; blood; urine; fluorescence; oxidative stress; human subject research; exposure; airborne particulate matter
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Graczyk Halshka, Lewinski Nastassja, Zhao Jiyuan, Concha-Lozano Nicolas, Riediker Michael, Characterization of Tungsten Inert Gas (TIG) Welding Fume Generated by Apprentice Welders, in Annals of Occupational Hygiene
The lungs are an excellent entry portal for gases and aerosol-transported molecules as they present a high surface area with thin epithelial barrier in addition to extensive vasculature. Nanoparticles (NPs) are studied for pulmonary administration of pharmaceutical agents since they present a longer retention time and allow for the prolonged release of loaded drugs. The same properties, however, pose a health risk for the case of non-medical NPs. NPs can transfer to novel target organs, and catalytically active NPs can generate oxidative stress, which can damage cells and launch a cascade of effects, contributing to acute and chronic diseases.The lung lining fluid is the initial point of contact for inhaled NPs. The processes in this liquid and the relation to other bodily liquids are essential for the understanding of the full chain of toxicological and pharmacokinetic events. We propose to study two main hypotheses:A)Inhaled nanoparticles that deposit in the lung become suspended in lung lining fluid and subsequently translocate into the circulation. B)Only reactive particles initiate an increase in oxidative stress in the lung lining fluid, which is then followed by an increase in oxidative stress markers in circulation and urine.We will address these hypotheses with the following specific activities:1)We will expose healthy non-smoking human volunteers to fluorescently labelled PVA-SPIONs (by inhalation) and quantitatively characterize the deposition and translocation of the PVA-SPIONs. Exhaled breath condensate will be collected as a surrogate of lung lining fluid and blood and urine will be collected to assess translocation into systemic circulation.2)We will expose the volunteers to reactive (tobacco smoke) in addition to the nonreactive (PVA-SPIONs) particles to demonstrate that there is a significant and clear difference between the levels of biomarkers of oxidative stress in the biological fluids of the different exposure groups.3)We will collect samples at several timepoints before and after exposure to study the timing of translocation and oxidative stress response in the different compartments and the correlation between these markers and the exposure levels.At the conclusion, we will have demonstrated the feasibility to study NPs in lung lining fluid and their translocation by collecting labeled SPIONs in EBC, blood and urine. We will also better understand how the oxidative stress response at the initial deposition site is linked to the systemic response and how this is reflected in urine.