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 Fenton catalyst to produce hydroxyl radical from hydrogen peroxide. Desferrioxamine (DF), an iron chelator, might inhibit the process of silica-induced pulmonary reaction. To test this assumption, we investigated the protective effect of DF on lipid peroxidation of cell membrane, production of inflammatory 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 malondialde-hyde (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-α (TNF-α) and interleukin-8 (IL-8) from A549, but also fibroblast proliferation. The therapeutic effect of DF on experimental silicosis in rat was also studied using total cell count with differential percentage in bronchoaiveoiar 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.