PHYTIC ACID, AN IRON CHELATOR, ATTENUATES PULMONARY INFLAMMATION AND FIBROSIS IN RATS AFTER INTRATRACHEAL INSTILLATION OF ASBESTOS

Reactive oxygen species, especially iron-catalyzed hydroxyl radicals ( . OH), are implicated in the pathogenesis of asbestos-induced pulmonar y toxicity. We previously demonstrated that phytic acid, an iron chela tor, reduces amosite asbestos-induced . OH generation, DNA strand brea k formation, and injury to cultured pulmonary epithelial cells (268 [1 995, Am. J. Physiol. (Lung Cell. Mel. Physiol.) 12: L471-480]). To det ermine whether phytic acid diminishes pulmonary inflammation and fibro sis in rats after a single intratracheal (it) instillation of amosite asbestos, Sprague-Dawley rats were given either saline (1 mi), amosite asbestos (5 mg; 1 mi saline), or amosite treated with phytic acid (50 0 mu M) for 24 hr and then instilled. At various times after asbestos exposure, the rats were euthanized and the lungs were lavaged and exam ined histologically. A fibrosis score was determined from trichrome-st ained specimens. As compared to controls, asbestos elicited a signific ant pulmonary inflammatory response, as evidenced by an increase (simi lar to 2-fold) in bronchoalveolar lavage (BAL) cell counts at 1 wk and the percentage of BAL neutrophils (PMNs) and giant cells at 2 wk (0.1 vs 6.5% and 1.3 vs 6.1%, respectively; p < 0.05). Asbestos significan tly increased the fibrosis score at 2 wk (0 + 0 vs 5 rf: 1;p < 0.05). The inflammatory and fibrotic changes were, as expected, observed in t he respiratory bronchioles and terminal alveolar duct bifurcations. Th e increased percentage of BAL PMNs and giant cells persisted at 4 wk, as did the fibrotic changes. Compared to asbestos alone, phytic acid-t reated asbestos elicited significantly less BAL PMNs (6.5 vs 1.0%; p < 0.05) and giant cells (6.1 vs 0.2%; p < 0.05) and caused significantl y less fibrosis (5 vs 0.8; p < 0.05) 2 wk after exposure. We conclude that asbestos causes pulmonary inflammation and fibrosis in rats after it instillation and that phytic acid reduces these effects. These dat a support the role of iron-catalyzed free radicals in causing pulmonar y toxicity from asbestos in vivo.