Development and characterization of a rapid-onset rodent inhalation model of asbestosis for disease prevention
Autor: | Joanne P. Marsh, Ruth Mickey, Jacqueline M. Doherty, Janet M. Petruska, Elliott Kagan, Marie A. Shatos, Kenneth B. Adler, Pamela M. Vacek, Ann Sesko, David Hemenway, Yvonne M. W. Janssen, Brooke T. Mossman |
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Rok vydání: | 1991 |
Předmět: |
Male
medicine.medical_specialty Pathology 040301 veterinary sciences Neutrophils Asbestosis Peptidyl-Dipeptidase A Toxicology medicine.disease_cause 030226 pharmacology & pharmacy Asbestos Pathology and Forensic Medicine 0403 veterinary science 03 medical and health sciences Hydroxyproline chemistry.chemical_compound 0302 clinical medicine Administration Inhalation Medicine Animals Molecular Biology Lung medicine.diagnostic_test Inhalation business.industry Superoxide Dismutase 04 agricultural and veterinary sciences Cell Biology respiratory system medicine.disease Alkaline Phosphatase Rats Inbred F344 respiratory tract diseases Rats Disease Models Animal Bronchoalveolar lavage medicine.anatomical_structure chemistry Alkaline phosphatase Histopathology business Bronchoalveolar Lavage Fluid |
Zdroj: | Toxicologic pathology. 19(4 Pt 1) |
ISSN: | 0192-6233 |
Popis: | A short-term inhalation model of asbestosis was developed in rodents to examine possible preventive approaches to lung disease. Fischer 344 (F344) rats were exposed for 10 and 20 days to National Institute of Environmental Health Sciences (NIEHS) crocidolite asbestos while sham controls were exposed to air only. To determine quantitative biochemical indicators of asbestos-induced lung disease, bronchoalveolar lavage (BAL) fluids were analyzed for lactic dehydrogenase (LDH), alkaline phosphatase, angiotensin-converting enzyme (ACE), and protein. Total and differential cell counts were performed on cell pellets from BAL. Lungs from additional rats were processed for histopathology, measurement of hydroxyproline, and autoradiography after injection of rats with 3H-thymidine. Exposure to asbestos for 10 and 20 days caused increases in LDH, alkaline phosphatase, and protein in BAL. In contrast, ACE was undetectable in BAL fluids from sham or asbestos-exposed rats. At both time periods, the percentages of polymorphonuclear leukocytes (PMNs) and lymphocytes in BAL were increased in asbestos-exposed rats. Total cell numbers in BAL were increased significantly at 20 days in animals inhaling asbestos. Exposure to asbestos for 10 and 20 days caused elevated amounts of hydroxyproline in lung and the development of fibrotic lesions. Asbestos-exposed rats exhibited increased numbers of interstitial cells and airspace epithelial cells incorporating 3H-thymidine, whereas labeled bronchiolar epithelial cells were not elevated significantly. The quantitative changes in asbestos-associated enzyme levels, cell types and protein in BAL, as well as increases in hydroxyproline and morphologic evidence of fibrosis, are useful indices of asbestos-related lung injury which enable preventive and therapeutic approaches to disease. |
Databáze: | OpenAIRE |
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