Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines.
Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines.
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DOI：
10.1186/1745-6673-5-29
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发表时间：
2010-10-27
期刊：
影响因子：
--
通讯作者：
Séralini GE
中科院分区：
文献类型：
--
作者：
Gasnier C;Benachour N;Clair E;Travert C;Langlois F;Laurant C;Decroix-Laporte C;Séralini GE
世界范围内使用的含有不同佐剂的农药，如农达配方，这是一种基于草甘膦的除草剂，可以在体内和人体细胞中引起一些毒性。这些农药通常存在于环境、地表水和耐农达转基因植物的食物残留物中。为了了解它们对主要解毒器官肝脏细胞的作用，我们研究了它们的作用机制和被称为Dig1的精确药用植物提取物的可能保护作用。采用人肝细胞系HepG2和Hep3B研究了四种草甘膦除草剂的细胞毒性途径，这是研究外源效应的已知模型。我们检测了线粒体琥珀酸脱氢酶和caspase 3/7的活性，以及细胞色素P450 1A1, 1A2, 3A4和2C9和谷胱甘肽- s转移酶对细胞死亡和保护的作用机制。所有四种农达制剂都会引起肝细胞死亡，佐剂的作用比单独使用草甘膦更强。Hep3B在48 h内的敏感性提高3-5倍。在非细胞毒性水平下，农达在HepG2中显著激活caspase 3/7，并可能诱导细胞凋亡并出现坏死。农达对CYP3A4的特异性增强作用比农业中使用的剂量少400倍（2%）。CYP1A2轻度升高，谷胱甘肽- s -转移酶（GST）下调。Dig 1无细胞毒性，本身不诱导caspase，能够在48 h内以时间依赖性的方式阻止农达诱导的细胞死亡，重要效率高达89%。此外，我们证明它可以阻止caspases 3/7的激活和CYP3A4的增强，而不是GST的降低，但反过来，在农达之前添加它可以轻微抑制CYP2C9。农达能够在不同程度上引起肝细胞系的细胞内破坏，但药用植物提取物Dig1的混合物可以在一定程度上保护人类细胞系免受这种污染物的侵害。所有这些系统构成了研究肝脏中毒和解毒的工具。
Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface waters and as food residues of Roundup tolerant genetically modified plants. In order to know their effects on cells from liver, a major detoxification organ, we have studied their mechanism of action and possible protection by precise medicinal plant extracts called Dig1. The cytotoxicity pathways of four formulations of glyphosate-based herbicides were studied using human hepatic cell lines HepG2 and Hep3B, known models to study xenobiotic effects. We monitored mitochondrial succinate dehydrogenase activity and caspases 3/7 for cell mortality and protection by Dig1, as well as cytochromes P450 1A1, 1A2, 3A4 and 2C9 and glutathione-S-transferase to approach the mechanism of actions. All the four Roundup formulations provoke liver cell death, with adjuvants having stronger effects than glyphosate alone. Hep3B are 3-5 times more sensitive over 48 h. Caspases 3/7 are greatly activated in HepG2 by Roundup at non-cytotoxic levels, and some apoptosis induction by Roundup is possible together with necrosis. CYP3A4 is specifically enhanced by Roundup at doses 400 times less than used in agriculture (2%). CYP1A2 is increased to a lesser extent together with glutathione-S-transferase (GST) down-regulation. Dig 1, non cytotoxic and not inducing caspases by itself, is able to prevent Roundup-induced cell death in a time-dependant manner with an important efficiency of up to 89%, within 48 h. In addition, we evidenced that it prevents Caspases 3/7 activation and CYP3A4 enhancement, and not GST reduction, but in turn it slightly inhibited CYP2C9 when added before Roundup. Roundup is able to provoke intracellular disruption in hepatic cell lines at different levels, but a mixture of medicinal plant extracts Dig1 can protect to some extent human cell lines against this pollutants. All this system constitutes a tool for studying liver intoxication and detoxification.
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4.5
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