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 α1-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. The increase of α1-proteinase inhibitor and blood glutathione can be considered a prompt protective response to the toxic injury.
Similar content being viewed by others
References
Adams JD Jr, Lauterburg BH, Mitchell JR (1983) Plasma glutathione and glutathione disulfide in the rat: Regulation and response to oxidative stress. J Pharmacol Exp Ther 227:749–754
Amoruso MA, Witz G, Goldstein BD (1981) Decreased superoxide anion radical by rat alveolar macrophages following inhalation of ozone or nitrogen dioxide. Life Sci 28:2215–2221
Boehme DS, Hotchkiss JA, Henderson RF (1992) Glutathione and GSH-dependent enzymes in bronchoalveolar lavage fluid cells in response to ozone. Exp Mol Pathol 56:37–48
Chow CK, Dillard CN, Tappel AL (1974) Glutathione peroxidase system and lysozime in rats exposed to ozone or nitrogen dioxide. Environ Res 7:311–319
DeNicola DB, Rebar AH, Henderson RF (1981) Early damage indicators in the lung. V. Biochemical and cytological responses to NO2 inhalation. Toxicol Appl Pharmacol 60:301–312
Evans MJ, Stephens RJ, Cabral LJ, Freeman G (1972) Cell renewal in the lungs of rats exposed to low levels of NO2. Arch Environ Health 24:180–188
Evans MJ, Cabral LJ, Stephens RJ, Freeman G (1973) Renewal of alveolar epithelium in the rat following exposure to NO2. Arch Environ Health 24:180–188
Evans MJ, Johnson LV, Stephens RJ, Freeman G (1976) Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3. Lab Invest 35:246–257
Federal Register (1978) 43:57601, Washington, DC
Freeman G, Haydon GB (1964) Emphysema after low-level exposure to NO2. Arch Environ Health 8:125–128
Freeman G, Crane SC, Stephens RJ, Furiosi NJ (1968) Pathogenesis of the nitrogen dioxide-induced lesion in the rat lung: A review and presentation of new observations. Am Rev Respir Dis 98:429–443
Gardner DE (1980) Influence of exposure patterns of nitrogen dioxide on susceptibility of infectious respiratory disease. Ann Arbor Sci, Ann Arbor, MI
Glasgow JE, Pietra GG, Abrams WR, Blank J, Oppenheim DM, Weinbaum G (1987) Neutrophil recruitment and degranulation during induction of emphysema in the rat by nitrogen dioxide. Am Rev Respir Dis 135:1129–1136
Ichinose T, Sagai M (1982) Studies on biochemical effects of nitrogen dioxide. III. Changes of the antioxidative protective systems in rat lungs and of lipid peroxidation by chronic exposure. Toxicol Appl Pharmacol 66:1–8
Johnson DA, Winters RS, Lee KR, Smith CE (1990) Oxidant effects on rat and human lung proteinase inhibitors. Res Resp Health Eff Inst 37:1–39
Johnson DA, Frampton MW, Winters RDS, Morrow PE, Utell MJ (1990) Inhalation of nitrogen dioxide fails to reduce the activity of human lung alpha-1-proteinase inhibitor. Am Rev Respir Dis 142:758–762
Johnston RB, Godzik CA, Cohn ZA (1978) Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med 148:115–127
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Fonil Phenol reagent. J Biol Chem 193:265–275
Parkinson DR, Stephens RJ (1973) Morphological surface changes in the terminal bronchiolar region of NO2 exposed rat lung. Environ Res 6:37–51
Postlethwait ME, Langford SD, Bidani A (1991) Transfer of NO2 through pulmonary epithelial lining fluid. Toxicol Appl Pharmacol 109:464–471
Robison TW, Duncan DP, Forman HJ (1990) Chemoattractant and leukotriene B4 production from rat alveolar macrophages exposed to nitrogen dioxide. Am J Respir Cell Mol Biol 3:21–26
Rose RM, Funglestad JM, Skornik WA, Hammer SM, Wolfthal SF, Beck BD, Brain JD (1988) The pathophysiology of enhanced susceptibility to murine cytomegalovirus respiratory infection during short term exposure to 5 ppm nitrogen dioxide. Am Rev Respir Dis 137:912–917
Sagai M, Ichinose T (1987) Lipid peroxidation and antioxidative protection mechanism in rat lungs upon acute and chronic exposure to nitrogen dioxide. Environ Health Perspec 73:179–189
Samet JM, Utell MJ (1990) The risk of nitrogen dioxide: what have we learned from epidemiological and clinical studies? Toxicol Ind Health 6:247–262
Stephens RJ, Freeman G, Crane SC, Furiosi N (1971) Ultrastructural changes in the terminal bronchiole of the rat during continuos, low level exposure to nitrogen dioxide. Exp Mol Pathol 14:1–19
Stephens RJ, Freeman G, Evans MJ (1972) Early response of lungs to low levels of nitrogen dioxide. Arch Environ Health 24:160–179
Weiss SJ (1989) Tissue destruction by neutrophils. Lancet 320 (6):365–376
Yoshida K, Kasama K (1987) Biotransformation of nitric oxide. Environ Health Perspec 73:201–206
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pagani, P., Romano, M., Erroi, A. et al. Biochemical effects of acute and subacute nitrogen dioxide exposure in rat lung and bronchoalveolar lavage fluid. Arch. Environ. Contam. Toxicol. 27, 426–430 (1994). https://doi.org/10.1007/BF00213182
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00213182