Potential role of free radicals in silicosis.
Vallyathan-V; Castranova-V; Pack-D; Leonard-S; Hubbs-A; Shumaker-J; Ducatman-B; Shoemaker-DA; Ramsey-D; Pretty-JR; McLaurin-JL; Khan-A; Stettler-LE; Teass-A; Weber-KC
FASEB J 1994 Apr; 8(5)(II):A666
Acute Silicosis is a fatal lung disease often associated with sandblasting, drilling, tunneling, and silica flour mill operations. We have shown recently that fracturing of silica generates free radicals on its cleavage planes, and that freshly fractured silica is more cytotoxicin in vitro than aged silica. The objective of this study was to determine if freshly fractured silica is biologically more active in vivo than aged silica in inducing lung injury in an animal model. Male pathogen-free Fischer 344 rats were exposed to freshly fractured or aged silica (20mg/m', 5 hr/day for 10 days). Silica dust was fractured by jet milling. The aged dust was stored for 60 days before use. Analysis of surface radicals on silica samples confirmed the increased concentration of radicals in fresh vs aged silica. Compared to aged silica, freshly fractured silica resulted in dramatically greater increases in cellular infiltrates, lactate dehydrogenase, B-N-acetyl glucosaminidase and decreases in anti-oxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase in alveolar macrophages (AM). AM induced enhanced oxygen radical generation, and pulmonary tissue showed increased lipid peroxidation in fresh vs aged silica-exposed animals. These results indicate that exposure to freshly fractured silica causes impairment of antioxidant defenses leading to acute Silicosis.
Silicates; Silica-dusts; Silicosis; Lung-disease; Lung-disorders; Lung-function; Lung-irritants; In-vivo-study; In-vitro-study; Free-radicals; Antioxidants; Laboratory-animals; Animal-studies; Animals
Abstract; Conference/Symposia Proceedings
The FASEB Journal. Experimental Biology '94, Anaheim, California, April 24-28, 1994