Approaches to prevention of asbestos-induced lung disease using polyethylene glycol (PEG)-conjugated catalase

Our plain-English summary of Approaches to prevention of asbestos-induced lung disease using polyethylene glycol (PEG)-conjugated catalase, by B.T. Mossman, J.P. Marsh, D. Hardwick, et al (Journal of Free Radicals in Biology & Medicine, 1986).

The study

• Authors: B.T. Mossman, J.P. Marsh, D. Hardwick, R. Gilbert, S. Hill, A. Sesko, M. Shatos, J. Doherty, A. Weller, M. Bergeron
• Journal: Journal of Free Radicals in Biology & Medicine
• Published: 1986;2(5-6):335-8
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos-associated damage to cells of the respiratory tract in vitro can be prevented by the simultaneous addition of scavengers of active oxygen species to cultures. To determine if administration of scavenger enzymes to animals and humans is a plausible approach to the prevention of asbestos-induced lung disease, osmotic pumps were filled with various concentrations of PEG-coupled catalase and implanted subcutaneously into Fischer 344 rats over a 28-day period. At 3, 14, and 28 days after implantation of the pumps, the animals were evaluated for levels of catalase in serum and lung. In addition, lung tissue and lavage fluids were examined at 28 days for biochemical and morphologic indications of cell injury, inflammation, and fibrotic lung disease. At all time points examined, the administration of PEG-catalase caused a dosage-dependent increase in serum levels of catalase. The levels of lung catalase were evaluated at 28 days but not at earlier time periods. In comparison to control rats, the amounts of enzymes (lactic dehydrogenase, alkaline phosphatase), protein, and cells in lavage fluids from treated animals were unaltered. Moreover, the lungs showed no evidence of inflammation or fibrotic disease as determined by differential cell counts in lavage and measurement of hydroxyproline. These studies suggest that administration of PEG-catalase does not cause injury or other alterations in lung tissue and can be pursued as a feasible approach to prevention of asbestosis.

In plain English

This was an animal experiment. The authors tested whether the antioxidant enzyme catalase, attached to polyethylene glycol (PEG-catalase), could be given to rats long-term without harming their lungs. Pumps under the skin of male Fischer 344 rats delivered 800, 4,000 or 8,000 IU of PEG-catalase per day for 28 days, with 4 rats per group per time point. Sham rats had surgery but no pump. No asbestos was used. Blood catalase rose with dose at 3, 14 and 28 days. In the Results, lung catalase was not significantly changed at 3 and 14 days but rose with dose at 28 days; the article's abstract instead says lung catalase was not evaluated before 28 days. At 28 days, enzyme and protein levels in fluid washed from the lungs of treated rats were not significantly raised, and total cell counts were unaltered compared with shams. Lung hydroxyproline, a measure of collagen, was lower at 800 IU per day for reasons the authors called unclear, but unchanged at higher doses. The authors concluded that giving PEG-catalase by pump was a feasible approach.

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: osmotic pumps delivering PEG-catalase were implanted under the skin of rats for 28 days and compared with sham-operated rats
• Who was studied: 200-g male Fischer 344 rats in three treatment groups plus sham controls, with 4 rats per group per time point (3, 14 and 28 days)
• Exposure: PEG-catalase at 800, 4,000 or 8,000 IU per day by subcutaneous osmotic pump. No asbestos exposure was part of this experiment. Sham rats had an incision but no pump.
• Main results:
  • Serum catalase rose with dose at all time points in treated rats.
  • According to the Results section, lung catalase was not significantly changed at 3 and 14 days. The article's abstract conflicts with this and says lung catalase was not evaluated at the earlier times.
  • Lung catalase showed a significant, dose-dependent increase at 28 days.
  • At 28 days, LDH, alkaline phosphatase and protein in lung lavage fluid from treated rats were not significantly raised above controls.
  • Lung hydroxyproline (collagen content) was decreased in rats receiving 800 U per day, for reasons the authors called unclear. It was not changed at the higher doses.
  • Total cell numbers in lavage fluid of treated rats were unaltered compared with sham controls.
  • In all groups, over 99% of lavage cells were macrophages, less than 0.6% were PMNs (a type of white blood cell) and less than 0.35% were lymphocytes.
• The authors' conclusion: The authors concluded that giving PEG-catalase to animals by osmotic pump is a feasible approach.

Topics

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

Medical terms in this study, explained in our Lexicon: Inflammation.

Related studies

• Inhibition of lung injury, inflammation, and interstitial pulmonary fibrosis by polyethylene glycol-conjugated catalase in a rapid inhalation model of asbestosis — B.T. Mossman, J.P. Marsh, et al. (1990)
• Prevention of asbestos-induced cell death in rat lung fibroblasts and alveolar macrophages by scavengers of active oxygen species — M.A. Shatos, J.M. Doherty, et al. (1987)
• Polyethylene glycol-superoxide dismutase, a conjugate in search of exploitation — F.M. Veronese, P. Caliceti, et al. (2002)
• Development and characterization of a rapid-onset rodent inhalation model of asbestosis for disease prevention — B.T. Mossman, Y.M. Janssen, et al. (1991)
• High levels of catalase and glutathione peroxidase activity dampen H2O2 signaling in human alveolar macrophages — A.B. Carter, L.A. Tephly, et al. (2004)
• Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage — S.J. Kim, P. Cheresh, et al. (2016)

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