LUNG INJURY AFTER SILICA INSTILLATION IS ASSOCIATED WITH AN ACCUMULATION OF IRON IN RATS

It has been postulated that the incomplete complexation of host iron b y the surface of mineral oxides is essential in in vivo lung injury af ter exposure to these dusts. We investigated the associations between in vivo iron accumulation after intratracheal instillation of silica d ust in rats and 1) concentrations of antioxidants and oxidized product s in the lung and 2) an index of chronic fibrotic injury. Fifty millig rams of minusil were intratracheally instilled into 60-day-old, male S prague-Dawley rats. Ionizable Fe3+ complexed to the surface of silica increased from 12.7 +/- 1.4 mu mol/g to values as high as 42.5 +/- 9.1 mu mol/g dust after instillation. Corresponding to this elevation of surface-adsorbed metal, concentrations of iron in bronchoalveolar lava ge fluid, lung tissue, plasma, and liver tissue all increased. Antioxi dant molecules in lung tissue, including ascorbate, urate, and glutath ione, 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 d epletion of iron stores before instillation of silica dust resulted in low iron stores (hematocrit values of 21.8 +/- 1.9) and low iron conc entrations in lavage fluid, lung tissue, and liver tissue. Rats on iro n-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.