EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON OXIDATIVE PATHWAYS IN A/J MICE
EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON OXIDATIVE PATHWAYS IN A/J MICE
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DOI：
10.1016/0891-5849(94)00099-6
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发表时间：
1995-01-01
影响因子：
7.4
通讯作者：
CASTONGUAY, A
中科院分区：
文献类型：
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作者：
BILODEAU, JF;WANG, MY;CASTONGUAY, A
烟草特有的N-亚硝胺，NNK，是实验室动物中的一种强效致癌物。作者先前已经表明，某些非甾体类抗炎药（NSAID），如舒林酸、布洛芬或吡罗昔康治疗可以显著降低A/J小鼠中NNK诱导的肺肿瘤发生。在这项研究中，作者研究了NSAID是否可以减少NNK诱导的氧化DNA损伤和/或抑制内源性脂质过氧化或A/J小鼠中的前列腺素E（2）（PGE（2））合成。在第一个实验中，用NNK（112 μ mol/kg B. w.）每周三次，同时维持在添加有布洛芬（263 mg/kg饮食）、萘普生（230 mg/kg）、舒林酸（123 mg/kg）、吡罗昔康（25 mg/kg）、吲哚美辛（5 mg/kg）或没有NSAID的饮食上。采用高效液相色谱-电子捕获检测器检测肺、肝组织DNA中8-OH-dG的含量。NSAID治疗对小鼠肺中内源性或NNK诱导的8-OH-dG形成无显著影响。在第二项实验中，A/J小鼠接受NSAID治疗2周后，通过测定肺组织中的硫代巴比妥酸反应物质（TBA-RS）来测定脂质过氧化反应，并通过酶免疫测定法测定血浆中的前列腺素E（2）水平。用某些非甾体抗炎药治疗可降低脂质过氧化水平和血浆PGE（2）水平，使其低于基础水平。综上所述，这些结果表明NSAID对NNK诱导的肺肿瘤发生的抑制更可能与前列腺素合成的抑制有关，而不是直接抑制NNK诱导的脂质过氧化或氧化DNA损伤。
The tobacco-specific N-nitrosamine, NNK, is a potent carcinogen in laboratory animals. The authors have shown previously that NNK-induced lung tumorigenesis in A/J mice can be reduced significantly by certain nonsteroidal antiinflammatory drugs (NSAIDs), such as sulindac, ibuprofen, or piroxicam treatments. In this study, the authors investigated whether NSAIDs could reduce NNK-induced oxidative DNA damage and/or inhibit endogenous lipid peroxidation, or prostaglandin E(2) (PGE(2)) synthesis in A/J mice. In the first experiment, A/J mice were gavaged with NNK (112 mu mol/kg b. w.) three times a week while being maintained on a diet to which either ibuprofen (263 mg/kg diet), naproxen (230 mg/kg), sulindac (123 mg/kg), piroxicam (25 mg/kg), indomethacin (5 mg/kg), or no NSAIDs had been added. Levels of 8-OH-dG in the DNA of lung and liver were measured by high-performance liquid chromatography with electron capture detector. Treatment with NSAIDs had no significant effects on the endogenous or NNK-induced formation of 8-OH-dG in the lung of the mice. In a second experiment, after treatment of A/J mice with NSAIDs for 2 weeks, lipid peroxidation was assayed by determining thiobarbituric acid-reactive substances (TBA-RS) in lung tissues, and prostaglandin E(2) levels were measured in plasma by an enzyme immunoassay. Treatments with some NSAIDs lowered the levels of lipid peroxidation and plasma levels of PGE(2) below basal levels. Taken together, these results suggest that the inhibition of NNK-induced lung tumorigenesis by NSAIDs is more likely related to an inhibition of prostaglandin synthesis than to a direct inhibition of lipid peroxidation or oxidative DNA damage induced by NNK.