title: Subchronic inhalation of zinc sulfate induces cardiac changes in healthy rats.
abstract: 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 microg/m(3) of aerosolized zinc sulfate (ZnSO(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.
authors.affiliation: Department of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, NC 27599, USA. wallenborn.grace@epa.gov
authors.forename: J Grace
authors.initials: JG
authors.lastname: Wallenborn
authors.forename: Paul
authors.initials: P
authors.lastname: Evansky
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Shannahan
authors.forename: Beena
authors.initials: B
authors.lastname: Vallanat
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.forename: Judy H
authors.initials: JH
authors.lastname: Richards
authors.forename: Reddy R
authors.initials: RR
authors.lastname: Gottipolu
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003600:Cytosol / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D019570:Inhalation Exposure; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D011921:Rats, Inbred WKY; D012137:Respiratory System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D019287:Zinc Sulfate / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D052638:Particulate Matter; D019287:Zinc Sulfate