Anti-malondialdehyde antibodies in MRL+/+ mice treated with trichloroethene and dichloroacetyl chloride: Possible role of lipid peroxidation in autoimmunity
Anti-malondialdehyde antibodies in MRL+/+ mice treated with trichloroethene and dichloroacetyl chloride: Possible role of lipid peroxidation in autoimmunity
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DOI：
10.1006/taap.2000.9086
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发表时间：
2001-01-15
影响因子：
3.8
通讯作者：
Ansari, GAS
中科院分区：
文献类型：
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作者：
Khan, MF;Wu, XH;Ansari, GAS
已知三氯乙烯（TCE）及其代谢物二氯乙酰氯（DCAC）之一在MRL+/+小鼠中诱导/加速自身免疫（AI）应答，如血清中的抗核、抗ssDNA、抗心磷脂和DCAC特异性抗体所证实的（Khan et al.，毒理学.应用药理学134，155-160，1995）。在本研究中，我们测量了TCE或DCAC处理的小鼠血清中的抗丙二醛抗体（AMDA），以了解脂质过氧化对AI反应的贡献。雌性MRL+/+小鼠（5周龄）每4天接受10 mmol/kg TCE或0.2 mmol/kg DCAC玉米油（100艾德）溶液ip注射，持续6周，而对照组仅接受等体积的溶剂，并通过本实验室建立的ELISA测定这些动物血清中的AMDA。虽然TCE治疗仅引起AMDA的边缘诱导，但DCAC治疗引起了显着的AMDA反应。此外，DCAC的时间-反应研究（0.2 mmol/kg，每4天，持续2、4、6或8周）显示，在治疗4周后诱导AMDA（3/4），在DCAC治疗6和8周时更大（5/5）。早在6周龄时，系统性红斑狼疮易感的MRL-lpr/lpr小鼠中就存在AMDA，进一步证实了这些发现。如本研究中所观察到的，AMDA的存在不仅表明脂质过氧化（氧化应激）增加，而且还表明氧化应激在炎症性自身免疫性疾病中的假定作用。(C)北京：科学出版社.
Trichloroethene (TCE) and one of its metabolites dichloroacetyl chloride (DCAC) are known to induce/accelerate autoimmune (AI) response in MRL+/+ mice as evident from anti-nuclear, anti-ssDNA, anti-cardiolipin, and DCAC-specific antibodies in the serum (Khan et al., Toxicol. Appl. Pharmacol. 134, 155-160, 1995). In the present study, we measured anti-malondialdehyde antibodies (AMDA) in the serum of TCE- or DCAC-treated mice in order to understand the contribution of lipid peroxidation to this AI response. Female MRL+/+ mice (5 weeks old) received ip injections of 10 mmol/kg TCE or 0.2 mmol/kg of DCAC in corn oil (100 Ed) every 4(th) day for 6 weeks, while controls received an equal volume of vehicle only, and AMDA was measured in the sera of these animals by an ELISA established in our laboratory. While TCE treatment caused only marginal induction of AMDA, DCAC treatment elicited a significant AMDA response. Furthermore, a time-response study of DCAC (0.2 mmol/kg, every 4(th) day, for 2, 4, 6, or 8 weeks) showed an induction of AMDA (3/4) after 4 weeks of treatment, which was even greater at both 6 and 8 weeks of DCAC treatment (5/5). These findings were further substantiated by the presence of AMDA in systemic lupus erythematosus-prone MRL-lpr/lpr mice as early as 6 weeks of age. Presence of AMDA, as observed in this study, not only indicates increased lipid peroxidation (oxidative stress), but also suggests a putative role of oxidative stress in inflammatory autoimmune diseases. (C) 2001 Academic Press.