Studies on the biochemical effects of nitrogen dioxide: IV. Relation between the change of lipid peroxidation and the antioxidative protective system in rat lungs upon life span exposure to low levels of NO 2

Abstract

This study examined the relation between lipid peroxidation and the antioxidative protective system in lungs of rats exposed to low levels of nitrogen dioxide (NO 2). JCL:male Wistar rats were exposed to 0, 0.04, 0.4, and 4 ppm NO 2 for 9, 18, and 27 months. Lipid peroxidation measured by TBA method, increased significantly in the 4 ppm NO 2 group of the 9-month exposure and in the 0.4 and 4 ppm NO 2 groups of the 18-month exposure. The activity of glutathione peroxidase measured with hydrogen peroxide as substrate decreased significantly in the 4 ppm NO 2 group of the 9-month exposure and in the 0.4 and 4 ppm NO 2 groups of the 18-month exposure. Furthermore, the activities of two glutathione S-transferases, aryl and aralkyl S-transferase, also decreased in the 0.4 and 4 ppm NO 2 groups of the 18-month exposure, but not in any groups of the 9-month exposure. The activity of glutathione peroxidase measured with cumene hydroperoxide as substrate did not show any significant changes in any NO 2 group. The activities of glucose-6-phosphate dehydrogenase and glutathione reductase were significantly higher than those in the control group for the 9-month exposure. In the 18-month exposure, however, they showed a tendency to return to control level. The activities of superoxide dismutase and disulfide reductase upon NO 2 exposure for 9 and 18 months were not different from control values. To confirm that lipid peroxidation was increased with greater NO 2 concentrations and exposure times, ethane and pentane exhalation in breath as an index of lipid peroxidation was examined. Ethane exhalation increased significantly following 0.04, 0.4, and 4 ppm NO 2 exposure for 9 and 18 months. Furthermore, ethane formation of rats exposed to 0.04 and 0.4 ppm NO 2 for 27 months also increased to twice the control level. On the other hand, after exposure to 4 ppm NO 2 for 27 months, ethane levels returned to control level. Pentane formation increased significantly only in the 0.04 and 0.4 ppm groups in the 18-month exposure. Ethane exhalation in rats exposed to 0.04, 0.12, and 0.4 ppm NO 2 for 9 and 18 months was similar. These results suggested that the antioxidative protective ability was decreased with prolonged exposure, while formation of cytotoxic lipid peroxides was increased. Furthermore, it was shown that in vivo lipid peroxidation, measured by ethane exhalation, was a good index of the biochemical effects induced by exposure to low levels of NO 2.