Oxidatively damaged DNA and inflammation in the liver of dyslipidemic ApoE-/- mice exposed to diesel exhaust particles
Oxidatively damaged DNA and inflammation in the liver of dyslipidemic ApoE-/- mice exposed to diesel exhaust particles
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DOI：
10.1016/j.tox.2007.05.009
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发表时间：
2007-07-31
期刊：
影响因子：
4.5
通讯作者：
Moller, Peter
中科院分区：
文献类型：
--
作者：
Folkmann, Janne Kjaersgaard;Risom, Lotte;Moller, Peter
流行病学研究表明，暴露于空气污染颗粒物与心血管疾病有关，而动脉粥样硬化的起始作用尚未得到解决。动脉粥样硬化被认为是一种炎症性疾病，也涉及氧化应激。在这里，我们研究了柴油机排气颗粒（DEP）引起的氧化应激在主动脉，肝脏和肺的血脂异常ApoE（-/-）小鼠的年龄时，可见斑块出现在主动脉（11-13周）的影响。通过腹膜内注射施用DEP（0、50、500和5000 μ g DEP/kg体重）以忽略继发于肺部炎症的血管效应。给药后6或24 h处死小鼠。通过诱导型一氧化氮合酶（iNOS）和血清一氧化氮的表达来测量炎症，并通过彗星试验测量DNA损伤。给药后6 h，肝脏中iNOSmRNA表达增加。在仅给予50 μ g/kg体重的小鼠中，24 μ g/kg剂量后，肝脏中的氧化嘌呤碱基水平（测定为甲酰胺嘧啶DNA糖基化酶位点）增加了67%（95%Cl：11-124%）。然而，没有迹象表明全身炎症确定为血清浓度的一氧化氮和iNOS的表达，和DNA损伤并没有增加在主动脉。这些观察结果表明，腹膜内注射DEP不会诱导肺和主动脉中的炎症或氧化损伤的DNA，而在血脂异常ApoE（-/-）小鼠的肝脏中观察到炎症和氧化DNA方面的直接影响。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Epidemiological studies have shown that exposure to air pollution particles is associated with cardiovascular diseases, whereas the role in the initiation of atherosclerosis is unresolved. Atherosclerosis is considered to be an inflammatory disease that also involves oxidative stress. Here we investigated effects of oxidative stress elicited by diesel exhaust particles (DEP) in the aorta, liver, and lung of dyslipidemic ApoE(-/-) mice at the age when visual plaques appear in the aorta (11-13 weeks). DEP was administrated by intraperitoneal injection (0, 50, 500 and 5000 mu g DEP/kg bodyweight) in order to omit vascular effects secondary to pulmonary inflammation. The mice were killed either 6 or 24 h after the administration. Inflammation was measured as the expression of inducible nitric oxide synthase (iNOS) and serum nitric oxide and DNA damage was measured by the comet assay. The expression of iNOS mRNA was increased in the liver 6 h after the administration. The level of oxidized purine bases, determined as formamidopyrimidine DNA glycosylase sites was increased by 67% (95% Cl: 11-124%) in the liver after 24 It in the mice administrated with only 50 mu g/kg bodyweight. However, there was no indication of systemic inflammation determined as the serum concentration of nitric oxide and iNOS expression, and DNA damage was not increased in the aorta. These observations indicate that intraperitoneal DEP injection does not induce inflammation or oxidatively damaged DNA in the lung and aorta, whereas a direct effect in terms of inflammation and oxidized DNA was observed in the liver of dyslipidemic ApoE(-/-) mice. (c) 2007 Elsevier Ireland Ltd. All rights reserved.