1 In previous studies a rat inhalation model was developed to investigate the effects of intervention after acute NO2 exposure. The object of the present study was to investigate whether acute NO2 intoxication induced comparable effects in rabbits as it does in rats. Where the effects of intervention in both species are similar, then the conclusions drawn from these studies may have more relevance for the treatment of man.
2 Biochemical variables in bronchoalveolar lavage and supernatant from lung homogenate, which may be relevant for the evaluation of lung injury and repair, were investigated and compared with histology.
3 After NO 2 exposure for 10 min, the pulmonary effects observed became more pronounced with increasing NO2 concentrations (0, 125, 175, 250, 400, 600 or 800 ppm) [1 ppm NO2 is 1.88 mg m-3]. The effects in rabbits were found to be broadly comparable with those in rats.
4 To achieve severe lung injury in rabbits without mortality, enabling investigations of the effects of intervention over several days, exposure to a NO2 concentration of 600 ppm for 10 min was most appropriate, while a concentration of 175 ppm NO2 was needed to attain comparable effects in rats.
5 The repair phase starts later, namely at 3 days after exposure in rats, compared to 5 days in rabbits.
Get full access to this article
View all access options for this article.
References
1.
Lowry T. & Schuman LMSilo-filler's disease: a syndrome caused by nitrogen dioxide. Journal of theAmerican Medical Association1956; 162: 153-60.
2.
Grayson RRSilage gas poisoning: nitrogen dioxide pneumonia, a new disease in agricultural workers. Annals of Internal Medicine1956; 45: 393-408.
3.
Moskowitz RL , Lyons HA, Cottle HPSilo-filler's disease: clinical, physiologic and pathologic study of a patient. American Journal of Medicine1964; 36: 457-62.
4.
Sangster B. & Meulenbelt J.Acute pulmonary intoxications. Overview and practical guidelines (review). NetherlandsJournal of Medicine1988; 33: 91-100.
5.
Meulenbelt J. & Sangster B.Acute nitrogen dioxide intoxication: clinical symptoms, pathophysiology and treatment (review). NetherlandsJournal of Medicine1990; 37: 132-8.
6.
Brown Rfr, Clifford WE, Marrs TC, Cox RAThe histopathology of rat lung following short term exposures to mixed oxides of nitrogen (NOx). BritishJournal of Experimental Pathology1983; 64: 579-93.
7.
Case BW, Gordon RE & Kleinerman J.Acute bronchiolar injury following nitrogen dioxide exposure: A freeze fracture study. Environmental Research1982; 29: 399-413.
8.
Guidotti TLToxic inhalation of nitrogen dioxide: morphologic and functional changes. Experimental andMolecular Pathology1980; 33: 90-103.
9.
DeNicola DB, Rebar AH & Henderson RFEarly damage indicators in the lung. V. Biochemical and cytological response to NO2 inhalation. Toxicology and Applied Pharmacology1981; 60: 301-12.
10.
Meulenbelt J., Dormans Jama, Marra M., Rombout Pja & Sangster B.Rat model to investigate the treatment of acute nitrogen dioxide intoxication. Human and Experimental Toxicology1992; 11: 179-87.
11.
Meulenbelt J., Bree van L., Dormans Jama, Boink Abtj & Sangster B.Biochemical and histological alterations in rats after acute nitrogen dioxide intoxication. Human and Experimental Toxicology1992; 11: 189-200.
12.
Siegel PD, Bozelka BE, Reynolds C. & George WJPhase-dependent response of the lung to NO2 irritant insult. Journal of Environmental Pathology, Toxicology and Oncology1989; 9: 303-15.
13.
Henderson RF , Rebar AH & DeNicola DB. Early damage indicators in the lungs. IV. Biochemical and cytologic response of the lung to lavage with metal salts. Toxicology and Applied Pharmacology1979; 51: 129-35.
14.
Beck BD, Brain JD & Bohannon DEAn in vivo hamster bioassay to assess the toxicity of particles for the lungs . Toxicology and Applied Pharmacology1982 ; 66: 9-29.
15.
Krieger B., Schwartz J., Loomis W., Marsh J. & Spragg R.Nonspecificity of elevated angiotensin-converting enzyme activity in bronchoalveolar lavage fluid from high permeability lung edema states. American Review of Respiratory Diseases1984; 129: 499-500.
16.
Evans MJ, Cabral LJ, Stephens RJ & Freeman G.Transformation of alveolar type II cells to type I cells following exposure to NO2. Experimental and Molecular Pathology1975; 22: 142-50.
17.
Evans MJ, Cabral-Anderson LJ & Freeman G.Role of the Clara cell in renewal of the bronchiolar epithelium. Laboratory Investigation1978; 38: 648-55.
18.
Henderson RFUse of bronchoalveolar lavage to detect lung damage. Environmental Health Perspectives1984; 56: 115-29.
19.
Henderson RF , Benson JM, Hahn FF, Hobbs CH, Jones RK, Mauderly JL, McClellan RO & Pickrell JANew approaches for the evaluation of pulmonary toxicity: bronchoalveolar fluid analysis. Fundamental and Applied Toxicology1985; 5: 451-8.
20.
Henderson RF , Damon EG & Henderson TREarly damage indicators in the lung. I. Lactate dehydrogenase activity in the airways. Toxicology and Applied Pharmacology1978; 44: 291-7.
21.
Henderson RF , Rebar AH, Pickrell JA & Newton GJEarly damage indicators in the lung. III. Biochemical and cytological response of the lung to inhaled metal salts. Toxicology and Applied Pharmacology1979; 50: 123-36.
