Approaches to prevention of asbestos-induced lung disease using polyethylene glycol (PEG)-conjugated catalase.
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.
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D001194:Asbestos / Q000633:toxicity*; D017638:Asbestos, Crocidolite; D001195:Asbestosis / Q000473:pathology / Q000517:prevention & control*; D002374:Catalase / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005609:Free Radicals; D007260:Infusion Pumps; D008168:Lung / Q000032:analysis / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344
D000975:Antioxidants; D005609:Free Radicals; D017638:Asbestos, Crocidolite; D001194:Asbestos; D011092:Polyethylene Glycols; D002374:Catalase