Effect of desferrioxamine on silica-induced pulmonary reaction

Surface iron on a mineral particle may be a major mediator of mineral-dust- induced toxicity, because iron on the surface of the particle acts as a Fen ton catalyst to produce hydroxyl radical from hydrogen peroxide. Desferriox amine (DF), an iron chelator, might inhibit the process of silica-induced p ulmonary reaction. To test this assumption, we investigated the protective effect of DF on lipid peroxidation of cell membrane, production of inflamma tory cytokine, and fibroblast proliferation by crystalline silica for an in vitro model. The Fenton activity of silica was decreased by preincubation with DF. Marked decreases in malondialdehyde (MDA) levels were seen in the DF-treated silica group compared with the untreated group. DF inhibited not only silica-induced release of tumor necrosis factor-alpha (TNF-alpha), an d interleukin-8 (IL-8) from A549, but also fibroblast proliferation. The th erapeutic effect of DF on experimental silicosis in rat was also studied us ing total cell count with differential percentage in bronchoalveolar lavage fluid the amount of hydroxyproline in lung and examination of a histologic section. DF significantly reduced inflammation and fibrosis compared with the untreated control. From these results, we concluded that DF might play a role in the inhibition of silica-induced pulmonary reaction.