Systemic translocation of 70Zinc: Kinetics following intratracheal instillation in rats

• Published in: Toxicology and applied pharmacology Vol. 234; no. 1; pp. 25 - 32
• Main Authors: Wallenborn, J. Grace, Kovalcik, Kasey D., McGee, John K., Landis, Matthew S., Kodavanti, Urmila P.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 2009; Elsevier
• Subjects: Air; Air pollution; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Chromosome aberrations; Environmental pollutants toxicology; Kinetics; Medical genetics; Medical sciences; Metals; Metals and various inorganic compounds; Toxicology; Translocation; Zinc; Translocation; Air pollution; Kinetics; Metals; Zinc; Chromosomal aberration; Rat; Rodentia; Transition metal; Systemic; Vertebrata; Mammalia; Animal; Cytogenetics; Abnormal chromosome; Chromosome translocation; Intratracheal administration
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2008.09.024

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 ( 64Zn, 66Zn, 67Zn, 68Zn, 70Zn), 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 μmol/rat 70Zn, using a solution enriched with 76.6% 70Zn. Natural abundance of 70Zn is 0.62%, making it an easily detectable tracer following exposure. In IT rats, lung 70Zn was highest 1 h post IT and declined by 48 h. Liver endogenous zinc was increased 24 and 48 h post IT. 70Zn was detected in all extrapulmonary organs, with levels higher following IT than following gavage. Heart 70Zn was highest 48 h post IT. Liver, spleen and kidney 70Zn peaked 4 h following gavage, and 24 h following IT. 70Zn IT exposure elicited changes in copper homeostasis in all tissues. IT instilled 70Zn translocates from lungs into systemic circulation. Route of exposure affects 70Zn 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.