Subchronic inhalation of zinc sulfate induces cardiac changes in healthy rats
- Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, ORD, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)
- Curriculum in Toxicology, UNC School of Medicine, Chapel Hill, NC 27599 (United States)
- Experimental Carcinogen Division, National Health and Environmental Effects Research Laboratory, ORD, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)
- Tel Aviv University, Tel Aviv (Israel)
Zinc is a common metal in most ambient particulate matter (PM), and has been proposed to be a causative component in PM-induced adverse cardiovascular health effects. Zinc is also an essential metal and has the potential to induce many physiological and nonphysiological changes. Most toxicological studies employ high levels of zinc. We hypothesized that subchronic inhalation of environmentally relevant levels of zinc would cause cardiac changes in healthy rats. To address this, healthy male WKY rats (12 weeks age) were exposed via nose only inhalation to filtered air or 10, 30 or 100 {mu}g/m{sup 3} of aerosolized zinc sulfate (ZnSO{sub 4}), 5 h/day, 3 days/week for 16 weeks. Necropsies occurred 48 h after the last exposure to ensure effects were due to chronic exposure rather than the last exposure. No significant changes were observed in neutrophil or macrophage count, total lavageable cells, or enzyme activity levels (lactate dehydrogenase, n-acetyl {beta}-D-glucosaminidase, {gamma}-glutamyl transferase) in bronchoalveolar lavage fluid, indicating minimal pulmonary effect. In the heart, cytosolic glutathione peroxidase activity decreased, while mitochondrial ferritin levels increased and succinate dehydrogenase activity decreased, suggesting a mitochondria-specific effect. Although no cardiac pathology was seen, cardiac gene array analysis indicated small changes in genes involved in cell signaling, a pattern concordant with known zinc effects. These data indicate that inhalation of zinc at environmentally relevant levels induces cardiac effects. While changes are small in healthy rats, these may be especially relevant in individuals with pre-existent cardiovascular disease.
- OSTI ID:
- 21144122
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 232, Issue 1; Other Information: DOI: 10.1016/j.taap.2008.05.025; PII: S0041-008X(08)00245-7; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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