This work was done to clarify the relationship between the changes of lipid peroxidation and the protective systems in lungs of rats exposed acutely, subacutely and chronically to nitrogen dioxide (NO
2).
In acute experiment, JCL: Wistar 8 week-old male rats were exposed continuously to 10 ppm NO
2 for 2 weeks. Lipid peroxidation, measured by ethane exhalation in the breath of the rats and by the reaction of thiobarbituric acid (TBA) with lung homogenates, increased to a maximum at the third day after a decline at the first day, and then returned to the initial level (of day 0).
Activities of glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), disulfide reductase (DSR), and superoxide dismutase (SOD) in the 105, 000 x g supernatant of lung homogenates were depressed slightly at the first day. There-.after, they increased significantly to their maximum levels from the 5th to 10th day, and these maximum levels were maintained until the 14th day. The pattern of change in these protective enzymes was symmetric to that of lipid peroxidation after the 3rd day. The order of the ratio of the increased value to the initial value was G6PD>DSR>6PGD>GR>GPx>SOD. The time course of non-protein sulfhydryls was similar to that of the protective enzymes. In contrast, the amounts of vitamin E increased to a maximum at the second day, and then returned to the initial level. The periodic change of vitamin E was similar to that of lipid peroxidation rather than that of the protective enzymes.
In subacute experiment, 13 week-old male rats were exposed continuously to 0.4, 1.2 and 4 ppm NO
2 for 1, 2, 4, 8, 12, and 16 weeks. Ethane exhalation increased to a maximum at the first week, and then returned to near the initial level at the 4th week. Thereafter, it showed a tendency toward gradual increase, again. TBA reactants in lung homogenates showed a similar pattern to that of ethane exhalation.
The activities of the antioxidative protective enzymes, i.e., glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), superoxide dismutase (SOD) and disulfide reductase (DSR) increased from the first week and reached their maximum levels at the 4th week, and then decreased gradually until the 16th week. The order of the increased ratios against the control group at the 4th week was G6PD>6PGD>GR>SOD>DSR>GPx, and the activities were dose-dependent against nitrogen dioxide levels of 0.4 to 4 ppm at each period. The contents of nonprotein sulfhydryls reached maximum levels at the 4th week, and the levels were maintained until the 16th week. The time course of vitamin E was similar to that of lipid peroxidation as measured by ethane exhalation rather than those of the protective enzymes.
In chronic experiments, 8 week-old male rats were exposed continuously to 0.04, 0.4 and 4 ppm NO
2 for 9, 18 and 27 months, Ethane exhalation increased significantly with 0.04, 0.4 and 4 ppm NO
2 exposure for 9 and 18 months, and dose-response relationship was clearly observed. Ethane exhalation of rats exposed to 0.04 and 0.4 ppm NO
2 for 27 months also increased two folds the control level. On the other hand, ethane exhalation of rats exposed to 4 ppm NO
2 for 27 months returned to the control level. Pentane exhalation was not so markable. TBA reactants in lungs also increased significantly in the 4 ppm NO
2 group at the 9th month, and in the 0.4 and 4 ppm NO
2 groups at the 18th month.
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