title: Differential pulmonary and cardiac effects of pulmonary exposure to a panel of particulate matter-associated metals.
abstract: Biological mechanisms underlying the association between particulate matter (PM) exposure and increased cardiovascular health effects are under investigation. Water-soluble metals reaching systemic circulation following pulmonary exposure are likely exerting a direct effect. However, it is unclear whether specific PM-associated metals may be driving this. We hypothesized that exposure to equimolar amounts of five individual PM-associated metals would cause differential pulmonary and cardiac effects. We exposed male WKY rats (14 weeks old) via a single intratracheal instillation (IT) to saline or 1 micromol/kg body weight of zinc, nickel, vanadium, copper, or iron in sulfate form. Responses were analyzed 4, 24, 48, or 96 h after exposure. Pulmonary effects were assessed by bronchoalveolar lavage fluid levels of total cells, macrophages, neutrophils, protein, albumin, and activities of lactate dehydrogenase, gamma-glutamyl transferase, and n-acetyl glucosaminidase. Copper induced earlier pulmonary injury/inflammation, while zinc and nickel produced later effects. Vanadium or iron exposure induced minimal pulmonary injury/inflammation. Zinc, nickel, or copper increased serum cholesterol, red blood cells, and white blood cells at different time points. IT of nickel and copper increased expression of metallothionein-1 (MT-1) in the lung. Zinc, nickel, vanadium, and iron increased hepatic MT-1 expression. No significant changes in zinc transporter-1 (ZnT-1) expression were noted in the lung or liver; however, zinc increased cardiac ZnT-1 at 24 h, indicating a possible zinc-specific cardiac effect. Nickel exposure induced an increase in cardiac ferritin 96 h after IT. This data set demonstrating metal-specific cardiotoxicity is important in linking metal-enriched anthropogenic PM sources with adverse health effects.
authors.affiliation: Department of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, NC 27599, USA. wallenbo@musc.edu
authors.forename: J Grace
authors.initials: JG
authors.lastname: Wallenborn
authors.forename: Mette J
authors.initials: MJ
authors.lastname: Schladweiler
authors.forename: Judy H
authors.initials: JH
authors.lastname: Richards
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005293:Ferritins / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019216:Metals, Heavy / Q000633:toxicity*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors
chemical_list: D000393:Air Pollutants; D019216:Metals, Heavy; D052638:Particulate Matter; D005293:Ferritins