The role of metals in particulate matter-induced toxicity: Cardiovascular effects of zinc.

摘要

Cardiovascular health effects following exposure to particulate matter (PM) are well recognized. One potential mechanism behind this is the direct translocation of water soluble PM components, including metals, from the lungs into the circulation, whereby they exert extrapulmonary effects directly. Zinc is a common PM-associated metal proposed to be a causative component in PM-induced injury. To further investigate this, three approaches have been taken. First, to assess the relative toxicity of zinc compared to other PM-associated metals, male Wistar Kyoto (WKY) rats (15 wks, 300-350 g) were exposed via a single intratracheal instillation (IT) to 1 mumol/kg body weight of saline or zinc, nickel, vanadium, iron or copper, all in soluble sulfate forms. Zinc induced specific pulmonary and cardiac effects, both in timing and degree of response. Second, to prove that zinc directly translocates from the lungs into systemic circulation following IT, we used high resolution magnetic sector field inductively coupled plasma mass spectrometry to measure levels of a stable isotope of zinc (70Zn) in lungs, plasma, heart, liver, spleen, and kidney of male WKY rats (13 wks, 250-300 g), 1, 4, 24, and 48 h following a single IT or oral gavage of saline or 0.7 mumol/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. Gavage group was included to distinguish between kinetics following pulmonary and oral exposure to zinc, as this dose is nontoxic when taken orally. 70Zn translocated to all extrapulmonary organs, with levels higher following IT than following gavage. Third, to ascertain whether cardiac changes occur following exposure to environmentally relevant levels of zinc, male WKY rats (12 wks age) were exposed via nose only inhalation to filtered air or 10, 30 or 100 mug/m3 of aerosolized zinc sulfate 5 h/d, 3 d/wk for 16 wks. No significant changes were observed in lung injury or inflammation markers, indicating minimal pulmonary effect; however in the heart, small but significant changes were detected. We have shown that soluble zinc directly moves from lungs into extrapulmonary systems, possibly in part causing PM-induced cardiovascular injury.