Systemic translocation of (70)zinc: kinetics following intratracheal instillation in rats.
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 ((64)Zn, (66)Zn, (67)Zn, (68)Zn, (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 micromol/rat (70)Zn, using a solution enriched with 76.6% (70)Zn. Natural abundance of (70)Zn is 0.62%, making it an easily detectable tracer following exposure. In IT rats, lung (70)Zn was highest 1 h post IT and declined by 48 h. Liver endogenous zinc was increased 24 and 48 h post IT. (70)Zn was detected in all extrapulmonary organs, with levels higher following IT than following gavage. Heart (70)Zn was highest 48 h post IT. Liver, spleen and kidney (70)Zn peaked 4 h following gavage, and 24 h following IT. (70)Zn IT exposure elicited changes in copper homeostasis in all tissues. IT instilled (70)Zn translocates from lungs into systemic circulation. Route of exposure affects (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.
Wallenborn
J Grace
JG
Department of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, NC 27599, USA. wallenborn.grace@epa.gov
Kovalcik
Kasey D
KD
McGee
John K
JK
Landis
Matthew S
MS
Kodavanti
Urmila P
UP
D000393:Air Pollutants / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000503:physiopathology; D003300:Copper / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007322:Instillation, Drug; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D052638:Particulate Matter / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors; D014018:Tissue Distribution; D014132:Trachea; D015033:Zinc Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000393:Air Pollutants; D052638:Particulate Matter; D015033:Zinc Isotopes; D003300:Copper