Multi-organ toxicity of ultrafine particles derived from air pollution: a sub-chronic exposure study in mice

Although air pollution-derived ultrafine particles (UFP) can reach extrapulmonary organs, current understanding of their distribution and toxicodynamics remains scarce and largely focused on the lung. In this work, we conducted, to the best of our knowledge, the first in vivo study using a multi-organ approach to assess both the toxicokinetics (i.e., biodistribution) and the toxicodynamics (i.e., oxidative stress, inflammation) of air pollution-derived UFP collected in an urban environment in mice sub-chronically exposed. The intrinsic oxidative potential (OP) of UFP was assessed prior to sub-chronic exposure of Balb/cJRj mice to 0, 10, or 30 μg of UFP/40 μL of sterile saline for 3 months. In the lungs, the heart, the liver, the kidneys, and the brain, oxidative stress was assessed by Nrf2 antioxidant cell signaling pathway activation, glutathione status, and oxidative damage, while NFкB-mediated inflammation was evaluated by specific cytokine secretion. UFP predominantly accumulate in the lung; however, these particles, together with their inorganic and/or organic components, can translocate into the bloodstream and reach highly vascularized extrapulmonary organs (i.e., heart, liver, kidneys, and brain). Owing to their high OP, UFP activated the Nrf2 antioxidant cell signaling pathway and the glutathione scavenging system, contributing to redox homeostasis in all the examined organs, particularly the lung and the brain, without inhibiting proinflammatory cytokine secretion. Taken together, these results highlighted the importance of considering both the biodistribution and the adverse health effects of UFP not only in the lung but also in extrapulmonary organs when assessing health risks.