Biochemical effects of combined gases of nitrogen dioxide and ozone. IV. Changes of lipid peroxidation and antioxidative protective systems in rat lungs upon life span exposure

Abstract

Lipid peroxide production, antioxidant contents and activities of antioxidative protective enzymes were examined in lungs of rats exposed to clean air (control group), 0.05 ppm O 3, 0.05 ppm O 3 + 0.04 ppm NO 2 and 0.05 ppm O 3 + 0.4 ppm NO 2 for 22 months. The results were compared with our previous data in rats exposed to 0.04 ppm NO 2, 0.4 ppm NO 2 and 4 ppm NO 2 for their life span (Sagai et al., Toxicol. Appl. Pharmacol., 73, (1984) 444–456). TBA values used as an index of lipid peroxidation in the lungs were increased maximally at 9 months, but were decreased below control values in animals exposed for 18 and 22 months. Nonprotein sulfhydryl (NPSH) contents were increased maximally at 9 months, and after 18 and 22 months were decreased significantly below values. Vitamin E (VE) contents showed a similar trend. On the other hand, enzyme activities of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione peroxidase measured by using cumene hydroperoxide (cum · OOH) substrate (GPx-cum · OOH), glutathione peroxidase measured by using H 2O 2 as a substrate (GPx-H 2O 2), glutathione S-transferase (GSH-Tase) and superoxide dismutase (SOD) did not show any significant changes during this experiment. The results show that lipid peroxidation in lungs was increased synergistically by a combination of NO 2 and O 3 at ambient levels, and that the time of maximum lipid peroxide production was shorter than with NO 2 alone. The protective ability against lipid peroxides was higher with increased lipid peroxide levels, but the inducibility was not maintained through a life span exposure to the combined gases. Additionally, two small adenomas were observed in 2 out of 18 rats in the 0.05 ppm O 3 + 0.04 ppm NO 2 group and a large adenoma was observed in 1 out of 18 animals in the 0.05 ppm + 0.4 ppm NO 2 group exposed for 22 months.