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IMMUNOTOXICITY OF PYRETHROID METABOLITES IN AN IN VITRO MODEL

机译:体外拟除虫菊酯代谢物的免疫毒性

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摘要

Risk assessment of man-made chemicals such as pesticides are mainly focused on parent compounds, and relatively little is known about their metabolites, especially with regard to target organ damages such as immunotoxicity. In the present study, the immunotoxicity of five synthetic pyrethroids (SPs) and three common metabolites was evaluated using an in vitro model by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cytoflow, and enzyme-linked immunosorbent assay (ELISA). Cell viability and apoptosis assays showed that both SPs and their metabolites possessed cytotoxicity to the monocytic cells. The aldehyde and acid derivatives were more effective than the other compounds at cytotoxicity, with inhibition of cell viability by 56.8 and 50.6% at 10~(-5) mol L~(-1), and induction of 8.52 and 8.81% cell apoptosis, respectively. Exposure to SPs and their metabolites also led to changes in the secretion levels of tumor necrosis factor a (TNF a) and interleukins (ILs), and again the metabolites showed stronger effects than the parent compounds. The aldehyde derivative upregulated IL- 12p70 level by 1.87-fold, and the alcohol and acid derivative increased the secretion of TNF a 5.88 and 7.96-fold, relative to the control group. In the in vitro model, the common metabolites of SPs clearly exerted greater immunotoxic effects to monocytes than the intact parent compounds. Results from the present study suggested the need for considering metabolites in achieving more comprehensive health risk assessment of man-made chemicals, including target organ toxicities such as immunotoxicity.
机译:农药等人造化学物质的风险评估主要集中在母体化合物上,对其代谢产物的了解相对较少,尤其是在靶器官损害(例如免疫毒性)方面。在本研究中,使用体外模型通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT)分析评估了五个合成拟除虫菊酯(SPs)和三个常见代谢物的免疫毒性。 ,细胞流和酶联免疫吸附测定(ELISA)。细胞活力和细胞凋亡检测表明,SP及其代谢产物均对单核细胞具有细胞毒性。醛和酸衍生物在细胞毒性方面比其他化合物更有效,在10〜(-5)mol L〜(-1)时,细胞活力分别抑制56.8和50.6%,并诱导8.52和8.81%的细胞凋亡,分别。暴露于SP及其代谢物也会导致肿瘤坏死因子a(TNF a)和白介素(ILs)的分泌水平发生变化,并且这些代谢物再次显示出比母体化合物更强的作用。相对于对照组,醛衍生物上调IL-12p70水平1.87倍,并且醇和酸衍生物使TNF的分泌增加5.88和7.96倍。在体外模型中,SP的常见代谢产物显然比完整的母体化合物对单核细胞具有更大的免疫毒性作用。本研究的结果表明,在对人造化学品进行更全面的健康风险评估时,需要考虑代谢产物,包括靶器官毒性,例如免疫毒性。

著录项

  • 来源
    《Environmental toxicology and chemistry》 |2010年第11期|p.2505-2510|共6页
  • 作者单位

    MOE Key Lab of Environmental Remediation and Ecosystem Health, Zhejiang University, Hangzhou 310027, People's Republic of China;

    rnResearch Center of Environmental Science, Zhejiang University of Technology, Hangzhou 310032, People's Republic of China;

    rnMOE Key Lab of Environmental Remediation and Ecosystem Health, Zhejiang University, Hangzhou 310027, People's Republic of China;

    rnResearch Center of Environmental Science, Zhejiang University of Technology, Hangzhou 310032, People's Republic of China;

    rnResearch Center of Environmental Science, Zhejiang University of Technology, Hangzhou 310032, People's Republic of China;

    rnMOE Key Lab of Environmental Remediation and Ecosystem Health, Zhejiang University, Hangzhou 310027, People's Republic of China,Research Center of Environmental Science, Zhejiang University of Technology, Hangzhou 310032, People's Republic of China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cytokine; cytotoxicity; metabolites; monocytes; pyrethroids;

    机译:细胞因子细胞毒性代谢物单核细胞;拟除虫菊酯;

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