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

Journal Article · Sun Nov 15 00:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.08.003· OSTI ID:21344788

Wallenborn, J. Grace, E-mail: [e-mail] ^[1]; Schladweiler, Mette J., E-mail: [e-mail] ^[2]; Richards, Judy H., E-mail: [e-mail] ^[2]; Kodavanti, Urmila P., E-mail: [e-mail] ^[2]

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1. Department of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, NC 27599 (United States)
2. Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, ORD, Environmental Protection Agency, Durham, NC 27711 (United States)

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 mumol/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.

• OSTI ID: 21344788
• Journal Information: Toxicology and Applied Pharmacology, Vol. 241, Issue 1; Other Information: DOI: 10.1016/j.taap.2009.08.003; PII: S0041-008X(09)00329-9; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALBUMINS
CHOLESTEROL
COPPER
FERRITIN
HEART
INFLAMMATION
INJURIES
IRON
LACTATE DEHYDROGENASE
LIVER
LUNGS
MACROPHAGES
METALLOTHIONEIN
NEUTROPHILS
NICKEL
RATS
TOXICITY
VANADIUM
ZINC
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARDIOVASCULAR SYSTEM
COMPLEXES
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
DISEASES
ELEMENTS
ENZYMES
GLANDS
HEMIACETAL DEHYDROGENASES
HYDROXY COMPOUNDS
IRON COMPLEXES
LEUKOCYTES
MAMMALS
MATERIALS
METALLOPROTEINS
METALS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PATHOLOGICAL CHANGES
PHAGOCYTES
PROTEINS
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
STEROIDS
STEROLS
SYMPTOMS
TRANSITION ELEMENT COMPLEXES
TRANSITION ELEMENTS
VERTEBRATES