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Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons

机译:新型农业杀菌剂对原代培养皮层神经元的毒性评估

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摘要

Fungicides are crucial for food protection as well as for the production of crops of suitable quality and quantity to provide a viable economic return. Like other pesticides, fungicides are widely sprayed on agricultural land, especially in wine-growing areas, from where they can move-off after application. Furthermore, residues of these agrochemicals can remain on crops after harvest and even after some food processing operations, being a major exposure pathway. Although a relatively low toxicity has been claimed for this kind of compounds, information about their neurotoxicity is still scarce. In the present study, nine fungicides recently approved for agricultural uses in the EU - ametoctradin, boscalid, cyazofamid, dimethomorph, fenhexamid, kresoxim-methyl, mepanipyrim, metrafenone and pyraclostrobin - have been evaluated for their toxicity in primary cultured mouse cortical neurons. Exposure to 0.1-100 μM for 7 days in vitro resulted in a dose-dependent toxicity in the MTT cell viability assay. Strobilurin fungicides kresoxim-methyl (KR) and pyraclostrobin (PY) were the most neurotoxic compounds (lethal concentration 50 were in the low micromolar and nanomolar levels, respectively) causing a rapid raise in intracellular calcium [Ca~(2+)]_i and strong depolarization of mitochondria] membrane potential. KR- and PY-induced cell death was reversed by the calcium channels blockers MK-801 and verapamil, suggesting that calcium entry through NMDA receptors and voltage-operated calcium channels are involved in KR- and PY-induced neurotoxicity. These results highlight the need for further evaluation of their neurotoxic effects in vivo.
机译:杀菌剂对于食品保护以及生产合适质量和数量的农作物以提供可行的经济回报至关重要。像其他农药一样,杀真菌剂被广泛喷洒在农田上,尤其是在葡萄种植区,施用后可从那里移走。此外,这些农用化学品的残留物在收获后甚至在某些食品加工操作之后仍可能残留在农作物上,这是主要的暴露途径。尽管已要求此类化合物具有较低的毒性,但有关其神经毒性的信息仍然很少。在本研究中,已评估了欧盟最近批准的9种杀真菌剂-阿米曲啶,boscalid,cyazofamid,dimethomorph,fenhexamid,kresoxim-methyl,mepanipyrim,metrafenone和吡咯菌酯-在原代培养的小鼠皮质神经元中的毒性。在体外暴露于0.1-100μM的7天导致MTT细胞活力测定中的剂量依赖性毒性。嗜球果伞素杀菌剂kresoxim-methyl(KR)和吡咯菌酯(PY)是最具神经毒性的化合物(致死浓度50分别处于低微摩尔和纳摩尔水平),引起细胞内钙[Ca〜(2 +)] _ i和线粒体膜的强去极化作用。钙通道阻滞剂MK-801和维拉帕米逆转了KR和PY诱导的细胞死亡,这表明钙通过NMDA受体和电压操纵的钙通道进入钙参与KR和PY诱导的神经毒性。这些结果突出了需要进一步评估它们在体内的神经毒性作用。

著录项

  • 来源
    《Environmental research》 |2015年第7期|37-44|共8页
  • 作者单位

    Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomediques de Barcelona (IIBB), Consejo Superior de Investigaciones Cientificas (CSIC), IDIBAPS, CIBERESP, Barcelona, Spain,Department of Analytical Chemistry and Food Science, Nutrition and Bromatology Group, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, Ourense, Spain;

    Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomediques de Barcelona (IIBB), Consejo Superior de Investigaciones Cientificas (CSIC), IDIBAPS, CIBERESP, Barcelona, Spain;

    Department of Analytical Chemistry and Food Science, Nutrition and Bromatology Group, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, Ourense, Spain;

    Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomediques de Barcelona (IIBB), Consejo Superior de Investigaciones Cientificas (CSIC), IDIBAPS, CIBERESP, Barcelona, Spain;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Cortical neurons; Fungicides; Neurotoxicity; Calcium channels; Mitochondrial membrane potential; Strobilurin;

    机译:皮质神经元;杀菌剂神经毒性钙通道;线粒体膜电位;球蛋白;

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