title: Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage.
abstract: Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM.
authors.affiliation: Department of Earth and Planetary Sciences, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Pardo
authors.affiliation: Flow Cytometry Unit, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Porat
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, and the National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Rudich
authors.affiliation: Environmental Chemistry and Technology Program, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Schauer
authors.affiliation: Department of Earth and Planetary Sciences, Weizmann Institute of Science, Rehovot, 76100, Israel. Electronic address: yinon.rudich@weizmann.ac.il.
authors.forename: Yinon
authors.initials: Y
authors.lastname: Rudich
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002947:Cities; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter
keywords: Air pollution; Inflammation; Intra-tracheal installation; Nrf2; Oxidative stress; Roadway metals