Time-course effects of antioxidants and phase II enzymes on diesel exhaust particles-induced oxidative damage in the mouse lung.
Mechanisms responsible for diesel exhaust particle (DEP)-induced toxicity in respiratory disorders are poorly understood, recent experimental and controlled exposure studies suggested that oxidative stress might be involved. To investigate the time-course effects DEP on nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator in cellular adaptive antioxidant response, mice were intratracheal instilled with 100 μg DEP/mouse and sacrificed after 30 min, 6 h, 12 h, 24 h, 48 h, and 72 h. We measured reactive oxygen species (ROS) as well as Nrf2 and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and phase II enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase-1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM) in the lungs. Additionally, histopathological changes were examined. At 6 h, ROS peaked, most of the enzymes were activated, and the histology showed the lungs were damaged. At 12 h, ROS returned to normal level and CAT activity decreased, while protein expression of Nrf2, HO-1, NQO1, GCLC, and GCLM increased, and the lungs were recovering from damage. After 24 h, ROS started to decrease and Nrf2 showed a decreasing trend at both gene and protein levels, while the lung damage had been entirely restored. These results suggested that a single exposure to DEP induce transient oxidative stress in the lungs, with time-dependent effects on Nrf2 and antioxidant enzymes and phase II enzymes.
['Zheng|Xiaomei|X|', 'Wang|Guanglei|G|', 'Bin|Ping|P|', 'Meng|Tao|T|', 'Niu|Yong|Y|', 'Yang|Mo|M|', 'Zhang|Liping|L|', 'Duan|Huawei|H|', 'Yu|Tao|T|', 'Dai|Yufei|Y|', 'Zheng|Yuxin|Y|']
D000818:Animals D000975:Antioxidants D004195:Disease Models, Animal D004798:Enzymes D015971:Gene Expression Regulation, Enzymologic D019570:Inhalation Exposure D008168:Lung D055370:Lung Injury D008297:Male D050217:Metabolic Detoxication, Phase II D008810:Mice, Inbred C57BL D051267:NF-E2-Related Factor 2 D018384:Oxidative Stress D052638:Particulate Matter D017382:Reactive Oxygen Species D013997:Time Factors D001335:Vehicle Emissions
Phase II enzymes Diesel exhaust particles Oxidative stress Antioxidant enzymes Time point