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 pulmonary toxicity. We previously demonstrated that phytic acid, an iron chelator, reduces amosite asbestos-induced .OH generation, DNA strand break formation, and injury to cultured pulmonary epithelial cells (268[1995, Am. J. Physiol.(Lung Cell. Mol. Physiol.) 12:L471-480]). To determine whether phytic acid diminishes pulmonary inflammation and fibrosis in rats after a single intratracheal (it) instillation of amosite asbestos, Sprague-Dawley rats were given either saline (1 ml), amosite asbestos (5 mg; 1 ml saline), or amosite treated with phytic acid (500 microM) for 24 hr and then instilled. At various times after asbestos exposure, the rats were euthanized and the lungs were lavaged and examined histologically. A fibrosis score was determined from trichrome-stained specimens. As compared to controls, asbestos elicited a significant pulmonary inflammatory response, as evidence by an increase (approximately 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 significantly increased the fibrosis score at 2 wk (0 +/- 0 vs 5 +/- 1; p < 0.05). The inflammatory and fibrotic changes were, as expected, observed in the respiratory bronchioles and terminal alveolar duct bifurcations. The increased percentage of BAl PMNs and giant cells persisted at 4 wk, as did the fibrotic changes. Compared to asbestos alone, phytic acid-treated 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 significantly 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 data support the role of iron-catalyzed free radicals in causing pulmonary toxicity from asbestos in vivo.
Kamp
D W
DW
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Israbian
V A
VA
Yeldandi
A V
AV
Panos
R J
RJ
Graceffa
P
P
Weitzman
S A
SA
D000818:Animals; D017639:Asbestos, Amosite / Q000008:administration & dosage / Q000633:toxicity*; D001195:Asbestosis / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005609:Free Radicals / Q000378:metabolism / Q000633:toxicity; D007442:Intubation, Intratracheal; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D010833:Phytic Acid / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005609:Free Radicals; D007502:Iron Chelating Agents; D017639:Asbestos, Amosite; D010833:Phytic Acid