Accumulation of iron in the rat lung after tracheal instillation of diesel particles.
Oxidant generation catalyzed by metals has been postulated to account for a lung injury following exposure to air pollution particles. In particles that are predominantly carbonaceous, it is difficult to implicate such an oxidative stress as the responsible mechanism, since concentrations of metals can be extremely low. Comparable to these air pollution particles, mineral oxide particles can include only minute amounts of metal, but lung injury following their exposure can be associated with an accumulation of endogenous iron from the host and an oxidative stress. We tested the hypothesis that diesel exhaust particulate (DEP) effects an accumulation of biologically active iron in the rat lung, with both oxidative stress and a lung injury resulting. Characterization of the DEP confirmed a high concentration of carbon, whereas metals were low in quantity. The concentration of total lavage iron in animals instilled with saline was low, but this concentration increased with exposure to DEP. Non-heme iron in lung tissue was similarly elevated after instillation of the diesel product. Particle instillation was associated with a decrease in lavage ascorbate concentration supporting an oxidative stress. Relative to saline exposure, DEP resulted in elevated lavage concentrations of the inflammatory mediators macrophage inflammatory protein-2 and tumor necrosis factor. Finally, an injury after particle instillation was evident with increased neutrophils and an elevation of lavage protein and lactic dehydrogenase. We conclude that DEP exposure effected an accumulation of iron in the rat lung. This accrual of iron was associated with an oxidative stress, release of oxidant-sensitive mediators, and a neutrophilic lung injury.
Ghio
A J
AJ
National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Richards
J H
JH
Carter
J D
JD
Madden
M C
MC
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D005293:Ferritins / Q000378:metabolism; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
D000393:Air Pollutants; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D005293:Ferritins; D007501:Iron