Systemic translocation of {sup 70}Zinc: Kinetics following intratracheal instillation in rats
- National Exposure Research Laboratory, ORD, Environmental Protection Agency, Durham, NC 27711 (United States)
- Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, ORD, Environmental Protection Agency, Durham, NC 27711 (United States)
Mechanisms of particulate matter (PM)-induced cardiotoxicity are not fully understood. Direct translocation of PM-associated metals, including zinc, may mediate this effect. We hypothesized that following a single intratracheal instillation (IT), zinc directly translocates outside of the lungs, reaching the heart. To test this, we used high resolution magnetic sector field inductively coupled plasma mass spectrometry to measure levels of five stable isotopes of zinc ({sup 64}Zn, {sup 66}Zn, {sup 67}Zn, {sup 68}Zn, {sup 70}Zn), and copper in lungs, plasma, heart, liver, spleen, and kidney of male Wistar Kyoto rats (13 weeks old, 250-300 g), 1, 4, 24, and 48 h following a single IT or oral gavage of saline or 0.7 {mu}mol/rat {sup 70}Zn, using a solution enriched with 76.6% {sup 70}Zn. Natural abundance of {sup 70}Zn is 0.62%, making it an easily detectable tracer following exposure. In IT rats, lung {sup 70}Zn was highest 1 h post IT and declined by 48 h. Liver endogenous zinc was increased 24 and 48 h post IT. {sup 70}Zn was detected in all extrapulmonary organs, with levels higher following IT than following gavage. Heart {sup 70}Zn was highest 48 h post IT. Liver, spleen and kidney {sup 70}Zn peaked 4 h following gavage, and 24 h following IT. {sup 70}Zn IT exposure elicited changes in copper homeostasis in all tissues. IT instilled {sup 70}Zn translocates from lungs into systemic circulation. Route of exposure affects {sup 70}Zn translocation kinetics. Our data suggests that following pulmonary exposure, zinc accumulation and subsequent changes in normal metal homeostasis in the heart and other organs could induce cardiovascular injury.
- OSTI ID:
- 21182688
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 234, Issue 1; Other Information: DOI: 10.1016/j.taap.2008.09.024; PII: S0041-008X(08)00398-0; 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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