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

Authors
Mossman-BT; Marsh-JP; Hardwick-D; Gilbert-R; Hill-S; Sesko-A; Shatos-M; Doherty-J; Weller-A; Bergeron-M
Source
J Free Radic Biol Med 1986 Jan; 2(5-6):335-338
NIOSHTIC No.
20037422
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.
Keywords
Asbestos-fibers; Lung-cells; Cell-damage; Cell-cultures; Cytotoxic-effects; Antioxidation; Oxidation-reduction-reactions; Free-radicals; Respiratory-system-disorders; In-vitro-studies; Laboratory-animals; Animal-studies; Author Keywords: Asbestos; Asbestosis; Lung injury; Oxygen free radicals; Lactic dehydrogenase; Alkaline phosphatase; PEG; Catalase
Contact
Pathology University of Vermont Burlington, VT 05405
CODEN
FRBMEH
Publication Date
19860101
Document Type
Journal Article
Funding Amount
97200
Funding Type
Grant
Fiscal Year
1986
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-K01-OH-00007
Issue of Publication
5-6
ISSN
0748-5514
Source Name
Journal of Free Radicals in Biology and Medicine
State
VT
Performing Organization
University of Vermont & St Agric College, Burlington, Vermont
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