Aj. Ghio et al., LUNG INJURY AFTER SILICA INSTILLATION IS ASSOCIATED WITH AN ACCUMULATION OF IRON IN RATS, American journal of physiology. Lung cellular and molecular physiology, 11(6), 1994, pp. 120000686-120000692
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.