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Pharmacologic manipulation of the murine pulmonary biochemical response to NO2.

Siegel-PD; George-WJ
J Environ Pathol Toxicol Oncol 1990 Jul; 10(4-5):231-236
A pharmacological investigation was conducted to examine the contribution of influxing neutrophils to the biochemical profile of the oxidant damaged lung, as well as suggest the probable sources and nature of several proliferative and tolerant phase biochemical indices of the pulmonary response to irritant insult. CD-1-mice were exposed to nitrogen-dioxide (10102440) (NO2) or filtered room air using a nose only inhalation chamber. Lung tissue was removed 2 days following an acute or extended subacute exposure protocol. Hydroxyurea (127071) was injected intraperitoneally on a daily basis at a dose of 200mg/kg for a total of 10 days. The last injection was given on the last day of exposure to NO2. In test mice this treatment induced granulocytopenia. The biochemical profile of hydroxyurea induced granulocytopenic mice, two days following an acute exposure to NO2, differed from normal mice in that the NO2 induced enhancement of both beta-glucuronidase and lactate- dehydrogenase activities was significantly attenuated in the granulocytopenic mice. However, hydroxyurea treatment did not affect basal levels or increases in choline-kinase activity, protease inhibitors, protein, or lung weight following acute exposure to NO2. The NO2 induced damage observed histopathologically was also not changed in the granulocytopenic mice. The only alteration in the response to NO2 following subacute exposure on hydroxyurea treated mice was a greater increase in the protease inhibitor activity in the granulocytopenic mice. From these results, the authors suggest that the biochemical profile of the lung exposed to NO2 may actually reflect the stage of the lung's dynamic response to injury, which correlates with the observable histopathology. They also suggest that the relative contribution of a particular source to the biochemical profile of the injured lung may vary with the stage of the response to the irritant. If the biochemical changes in the lung are reflected in lavage fluid or serum, evaluation of enzymatic/nonenzymatic markers may be a useful tool in assessing alveolar damage.
NIOSH-Author; Oxides; Nitrogen-oxides; Laboratory-animals; Lung-cells; Respiratory-system-disorders; Inhalation-studies; Inhalants; Toxic-gases; In-vivo-study
10102-44-0; 127-07-1
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Journal of Environmental Pathology, Toxicology and Oncology