AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 6 686-L692, Copyright © 1994 by American Physiological Society
Lung injury after silica instillation is associated with an accumulation of iron in rats
A. J. Ghio, R. H. Jaskot and G. E. Hatch
Durham Veterans Affairs Medical Center, North Carolina.
It has been postulated that the incomplete complexation of host iron by the
surface of mineral oxides is essential in in vivo lung injury after
exposure to these dusts. We investigated the associations between in vivo
iron accumulation after intratracheal instillation of silica dust in rats
and 1) concentrations of antioxidants and oxidized products in the lung and
2) an index of chronic fibrotic injury. Fifty milligrams of minusil were
intratracheally instilled into 60-day-old, male Sprague-Dawley rats.
Ionizable Fe3+ complexed to the surface of silica increased from 12.7 +/-
1.4 mumol/g to values as high as 42.5 +/- 9.1 mumol/g dust after
instillation. Corresponding to this elevation of surface-adsorbed metal,
concentrations of iron in bronchoalveolar lavage fluid, lung tissue,
plasma, and liver tissue all increased. Antioxidant molecules in lung
tissue, including ascorbate, urate, and glutathione, all decreased, whereas
superoxide dismutase increased. Oxidized products in the lung tissue,
measured as thiobarbituric acid-reactive products, similarly increased,
reflecting an oxidant stress. Dietary depletion of iron stores before
instillation of silica dust resulted in low iron stores (hematocrit values
of 21.8 +/- 1.9) and low iron concentrations in lavage fluid, lung tissue,
and liver tissue. Rats on iron-depleted diets demonstrated a diminished
fibrotic injury after dust instillation. Complexation of iron by the dust
surface may be central in collagen deposition after silica exposure.
