Differential pulmonary and cardiac effects of pulmonary exposure to a panel of particulate matter-associated metals

• Published in: Toxicology and applied pharmacology 2009-11, Vol.241 (1), p.71-80
• Main Authors: Wallenborn, J. Grace, Schladweiler, Mette J., Richards, Judy H., Kodavanti, Urmila P.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Air; Air Pollutants - toxicity; Air Pollution; ALBUMINS; ANIMAL CELLS; ANIMALS; Biological and medical sciences; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; Bronchoalveolar Lavage Fluid; Cardiovascular; CARDIOVASCULAR SYSTEM; Chemical and industrial products toxicology. Toxic occupational diseases; CHOLESTEROL; COMPLEXES; CONNECTIVE TISSUE CELLS; COPPER; Cytosol - drug effects; Cytosol - metabolism; DIGESTIVE SYSTEM; DISEASES; ELEMENTS; Environmental pollutants toxicology; ENZYMES; FERRITIN; Ferritins - drug effects; Ferritins - metabolism; Gene Expression Regulation - drug effects; GLANDS; HEART; Heart - drug effects; HEMIACETAL DEHYDROGENASES; HYDROXY COMPOUNDS; INFLAMMATION; Inflammation - chemically induced; INJURIES; IRON; IRON COMPLEXES; LACTATE DEHYDROGENASE; LEUKOCYTES; LIVER; Liver - drug effects; Liver - metabolism; Lung - drug effects; Lung - metabolism; LUNGS; MACROPHAGES; Male; MAMMALS; MATERIALS; Medical sciences; METALLOPROTEINS; METALLOTHIONEIN; METALS; Metals and various inorganic compounds; Metals, Heavy - toxicity; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; NEUTROPHILS; NICKEL; ORGANIC COMPOUNDS; ORGANS; OXIDOREDUCTASES; Particulate matter; Particulate Matter - toxicity; PATHOLOGICAL CHANGES; PHAGOCYTES; PROTEINS; RATS; Rats, Inbred WKY; RESPIRATORY SYSTEM; RODENTS; SOMATIC CELLS; STEROIDS; STEROLS; SYMPTOMS; Time Factors; TOXICITY; Toxicology; TRANSITION ELEMENT COMPLEXES; TRANSITION ELEMENTS; VANADIUM; VERTEBRATES; ZINC
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2009.08.003

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 μmol/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, γ-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.