Biochemical effects of acute and subacute nitrogen dioxide exposure in rat lung and bronchoalveolar lavage fluid

Abstract

The pulmonary inflammatory response to NO2 exposure was measured by evaluating a series of biochemical and cellular parameters in rat bronchoalveolar lavage fluid. Animals were exposed to 9 mg/m3 (5 ppm) or 18 mg/m3 (10 ppm) of the gas for 24 h or 7 days. After bronchoalveolar lavage collection, a differential count of polymorphonuclear leukocytes, macrophages, and lymphocytes was done. A significant increase in polymorphonuclear leukocytes was found after 24 h of exposure, and after 7 days the number of macrophages increased significantly. After 7 days of exposure to 9 mg/m3 of NO2 (a dose that under our conditions did not induce migration of cells in the bronchoalveolar spaces) the ex vivo phorbol myristate acetate-induced superoxide anion production by resident cells was inhibited. After 24 h and 7 days of exposure to 18 mg/m3 of NO2, phorbol myristate acetate-induced superoxide anion production was lower than in the control group. The migration of polymorphonuclear leukocytes in the bronchoalveolar lavage fluid was not associated with any real increase in elastase. However, there was a dose- and time-dependent increase in alpha 1-proteinase inhibitor in response to both 9 and 18 mg/m3 of NO2. Total glutathione was significantly increased in blood by 24 h treatment with 9 or 18 mg/m3 of NO2, whereas blood oxidized glutathione was not affected. In lung tissue we observed only a significant increase of oxidized glutathione after 24 h of exposure to 9 and 18 mg/m3 of NO2. These data suggest that many biochemical and cellular parameters are altered after acute or subacute exposure to relatively high doses of NO2, especially in the first 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)