Sagai M, Ichinose T, Kubota K
Toxicol Appl Pharmacol. 1984 May;73(3):444-56. doi: 10.1016/0041-008x(84)90097-8.
This study examined the relation between lipid peroxidation and the antioxidative protective system in lungs of rats exposed to low levels of nitrogen dioxide (NO2). JCL:male Wistar rats were exposed to 0, 0.04, 0.4, and 4 ppm NO2 for 9, 18, and 27 months. Lipid peroxidation measured by TBA method, increased significantly in the 4 ppm NO2 group of the 9-month exposure and in the 0.4 and 4 ppm NO2 groups of the 18-month exposure. The activity of glutathione peroxidase measured with hydrogen peroxide as substrate decreased significantly in the 4 ppm NO2 group of the 9-month exposure and in the 0.4 and 4 ppm NO2 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 NO2 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 NO2 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 NO2 exposure for 9 and 18 months were not different from control values. To confirm that lipid peroxidation was increased with greater NO2 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 NO2 exposure for 9 and 18 months. Furthermore, ethane formation of rats exposed to 0.04 and 0.4 ppm NO2 for 27 months also increased to twice the control level. On the other hand, after exposure to 4 ppm NO2 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 NO2 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.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究检测了低水平二氧化氮(NO₂)暴露大鼠肺组织中脂质过氧化与抗氧化保护系统之间的关系。日本清洁动物中心的雄性Wistar大鼠分别暴露于0、0.04、0.4和4 ppm的NO₂环境中9、18和27个月。采用TBA法测定脂质过氧化水平,结果显示,9个月暴露组中4 ppm NO₂组以及18个月暴露组中0.4和4 ppm NO₂组的脂质过氧化水平显著升高。以过氧化氢为底物测定谷胱甘肽过氧化物酶活性,结果显示,9个月暴露组中4 ppm NO₂组以及18个月暴露组中0.4和4 ppm NO₂组的该酶活性显著降低。此外,18个月暴露组中0.4和4 ppm NO₂组的两种谷胱甘肽S-转移酶(芳基和芳烷基S-转移酶)活性也降低,但9个月暴露组中各NO₂组均未出现此现象。以氢过氧化异丙苯为底物测定谷胱甘肽过氧化物酶活性,结果显示各NO₂组均未出现显著变化。9个月暴露组中,葡萄糖-6-磷酸脱氢酶和谷胱甘肽还原酶活性显著高于对照组。然而,在18个月暴露组中,它们有恢复至对照水平的趋势。9个月和18个月NO₂暴露后,超氧化物歧化酶和二硫还原酶活性与对照值无差异。为证实脂质过氧化随NO₂浓度升高和暴露时间延长而增加,检测了呼出气体中乙烷和戊烷的呼出量作为脂质过氧化指标。9个月和18个月的0.04、0.4和4 ppm NO₂暴露后,乙烷呼出量显著增加。此外,27个月的0.04和0.4 ppm NO₂暴露大鼠的乙烷生成量也增加至对照水平的两倍。另一方面,27个月的4 ppm NO₂暴露后,乙烷水平恢复至对照水平。仅在18个月暴露组的0.04和0.4 ppm组中,戊烷生成量显著增加。9个月和18个月的0.04、0.12和0.4 ppm NO₂暴露大鼠的乙烷呼出量相似。这些结果表明,随着暴露时间延长,抗氧化保护能力下降而细胞毒性脂质过氧化物的生成增加。(摘要截选至400字)