Effect of Desferrioxamine on Silica-Induced Cytotoxicity of A549 and Fibroblast Proliferation / 대한산업의학회지

ABSTRACT

The inhalation of crystalline silica results in the production of reactive oxygen species(ROS). Among these ROS, hydroxyl radical( OH) is believed to be the most reactive one. OH is generated in reaction between superoxide and hydrogen peroxide catalyzed by transition metal, especially iron. Therefore iron should be important in the bioactivity of crystalline silica. Desferrioxamine, a iron chelator, may be protective in silica-induced pulmonary reaction. To test this assumption we investigated the protective effect of desferrioxamine on lipid peroxidation of cell membrane, cytotoxicity, production of proinflammatory and chemotactic cytokine and fibroblast proliferation by crystalline silica in vitro model. The results were as follows: 1. Fenton activity of silica and asbestos was significantly higher than that of control. Fenton activity in crocidolite was higher than silica at the same dose. This result correlated with iron content of dust. Fenton activity of silica and crocidolite was decreased by preincubation of silica with desferrioxamine. 2. Silica induced a dose-dependent increase of MIDA concentration in lung epithelial cell lysate dose dependently. Marked decrease of MDA was observed in desferrioxaminetreated silica group compared with untreated group. 3. As concentration of stimulated silica, silica?induced cytotoxicity was increased. There was significant decrease of cytotoxicity in desferrioxamine?treated silica group compared with untreated group. 4. a-quartz augmented the production of TNF-a and IL-8 from A549 cell. While desferrioxa-mine suppressed the release of cytokines. 5. Supernatant of silica-cocultured A549 cell induced a significant proliferation of fibroblast, which desferrioxaime blocked this proliferation. From these result, we concluded that desferrioxamine has a protective effect on silica induced pulmonary reaction.