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Subchronic inhalation of zinc sulfate induces cardiac changes in healthy rats
Citation:
WALLENBORN, G., P. A. EVANSKY, J. H. Shannahan, B. VALLANAT, A. D. LEDBETTER, M. SCHLADWEILER, J. E. RICHARDS, R. R. Gottipolu, A. Nyska, AND U. P. KODAVANTI. Subchronic inhalation of zinc sulfate induces cardiac changes in healthy rats. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 1(232):69-77, (2008).
Impact/Purpose:
This is a toxicological study conducted in rats to demonstrate the role of particle-associated zinc in cardiac injury. Rats were exposed via nose-only inhalation to zinc sulfate aerosol at environmentally relevant concentrations and pulmonary and cardiovascular responses were analyzed.
Description:
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 question, healthy male WKY rats (12 wks age) were exposed via nose only inhalation to filtered air or 10, 30 or 100 µg/m3 of aerosolized zinc sulfate (ZnSO4), 5 h/d, 3 d/wk for 16 wks. 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 β-D-glucosaminidase, γ-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.
