Phytic acid, an iron chelator, attenuates pulmonary inflammation and fibrosis in rats after intratracheal instillation of asbestos

Our plain-English summary of Phytic acid, an iron chelator, attenuates pulmonary inflammation and fibrosis in rats after intratracheal instillation of asbestos, by D.W. Kamp, V.A. Israbian, A.V. Yeldandi, et al (Toxicologic Pathology, 1995).

The study

• Authors: D.W. Kamp, V.A. Israbian, A.V. Yeldandi, R.J. Panos, P. Graceffa, S.A. Weitzman
• Journal: Toxicologic Pathology
• Published: 1995;23(6):689-95
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This was an animal experiment in male Sprague-Dawley rats. Rats received one dose into the windpipe (intratracheal instillation) of saline, 5 mg of amosite asbestos, or amosite pretreated for 24 hours with phytic acid, an iron-binding substance; two rats received phytic acid alone. Saline and asbestos groups were examined at 1, 2 and 4 weeks, phytic acid groups at 2 weeks only, usually 3 to 5 rats per group. Compared with controls, asbestos raised the percentage of neutrophils and giant cells in lung-washing (lavage) fluid about 5- to 11-fold through 4 weeks. Fibrosis scores were 0 in controls versus 5.3 at 2 weeks and 2.0 at 4 weeks after asbestos. At 2 weeks, phytic acid-treated asbestos produced fewer neutrophils (1.0% versus 6.5%), fewer giant cells (0.2% versus 6.1%) and less fibrosis (0.8 versus 5) than untreated asbestos. Fibrosis was still mildly but statistically significantly higher than in controls (0.8 versus 0; p = 0.013). The authors concluded phytic acid reduced these effects, supporting a role for iron-catalyzed free radicals. They noted that long-term effects were untested and that inhalation models better match human exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: a single intratracheal instillation in rats, comparing saline, amosite asbestos, and phytic acid-pretreated amosite groups, plus a small phytic acid-alone group
• Who was studied: Male Sprague-Dawley rats (250-300 g). Saline and asbestos groups were examined at 1, 2 and 4 weeks after exposure. The phytic acid-treated asbestos group and the phytic acid-alone group (n = 2) were examined at 2 weeks. Group sizes were generally 3 to 5 rats.
• Exposure: A single intratracheal instillation of one of the following: phosphate-buffered saline (1 ml); amosite asbestos (5 mg in 1 ml PBS, UICC reference sample); amosite pretreated with 500 micromolar phytic acid (an iron chelator) for 24 hours; or phytic acid alone
• Main results:
  • At 1 week, total lavage cell counts were 7.4 plus or minus 1.5 million in asbestos-exposed rats (n = 4) versus 3.7 plus or minus 1.1 million in controls (n = 3), p = 0.06. At 2 and 4 weeks the counts were similar in the two groups.
  • Compared with controls, amosite increased the percentage of lavage neutrophils and multinucleated giant cells by about 5- to 11-fold, and the differences persisted over 4 weeks.
  • Asbestos caused a mild rise in lavage protein at 2 and 4 weeks that was not statistically significant.
  • Fibrosis scores, controls vs asbestos, were 0 vs 5.3 plus or minus 0.7 at 2 weeks and 0 vs 2.0 plus or minus 0 at 4 weeks (p less than 0.05). At 1 week there was only a trend: 0 vs 1.5 plus or minus 0.9 (p = 0.12).
  • In asbestos-exposed rats, fibrotic changes were mainly in areas of fiber deposition, including the terminal respiratory bronchioles and alveolar duct bifurcations.
  • The phytic acid comparison was made 2 weeks after instillation.
  • At 2 weeks, phytic acid-treated asbestos produced significantly fewer lavage neutrophils than untreated asbestos (6.5 vs 1.0%, asbestos vs phytic acid-treated asbestos).
  • At 2 weeks, phytic acid-treated asbestos produced significantly fewer lavage giant cells than untreated asbestos (6.1 vs 0.2%).
  • At 2 weeks, phytic acid-treated asbestos caused significantly less fibrosis than untreated asbestos (fibrosis score 5 vs 0.8).
  • Compared with controls, phytic acid-treated asbestos still caused a mild but statistically significant increase in fibrosis score at 2 weeks (0 vs 0.8 plus or minus 0.2; p = 0.013).
  • Phytic acid alone (n = 2) did not cause an inflammatory or fibrotic response at 2 weeks.
• The authors' conclusion: The authors concluded that intratracheal amosite asbestos causes pulmonary inflammation and fibrosis in rats and that phytic acid reduces these effects. In their view, the data support a role for iron-catalyzed free radicals in asbestos lung toxicity.
• Limitations the authors state:
  • The study did not address where the redox-active iron came from, or whether phytic acid has any long-term beneficial effect.
  • The precise mechanism by which phytic acid reduced asbestos toxicity was not defined.
  • The instillation model was a possible limitation: inhalation models are more physiologically relevant to human exposure and may give a more even distribution of fibers in the lung.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Asbestosis.

Medical terms in this study, explained in our Lexicon: Inflammation, Fibrosis, Reactive Oxygen Species (ROS), Hydroxyl Radical, Amosite, Asbestos Exposure, Bronchoalveolar Lavage (BAL).

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