Several investigators demonstrated that glyphosate formulations produce neurotoxicity associated with oxidative stress, alterations in glutamatergic system, inhibition of acetylcholinesterase activity and mitochondrial dysfunction. However, the underlying molecular mechanisms following exposure to this herbicide on astrocytes are unclear. Thus, the aim of the present study was to determine the activity of enzymes related to energy metabolism, in addition to oxidative stress parameters, mitochondrial mass, nuclear area, and autophagy in astrocytes treated with a glyphosate-based herbicide. Our results showed that 24 h exposure to a glyphosate-based herbicide decreased (1) cell viability, (2) activities of mitochondrial respiratory chain enzymes and creatine kinase (CK), (3) mitochondrial mass, and (4) nuclear area in rat astroglioma cell line (C6 cells). However, non-protein thiol (NPSH) levels were increased but catalase activity was not changed in cells exposed to the herbicide at non-cytotoxic concentrations. Low glyphosate concentrations elevated content of cells positive to autophagy-related proteins. Nuclear factor erythroid 2-related factor (Nrf2), NAD(P)H dehydrogenase [quinone] 1 (NQO1) and PTEN-induced kinase 1 (PINK1) labeling were not markedly altered in cells exposed to glyphosate at the same concentrations that an increase in NPSH levels and positive cells to autophagy were found. It is conceivable that mitochondria and CK may be glyphosate-based herbicides targets. Further, autophagy induction and NPSH increase may be mechanisms initiated to avoid oxidative stress and cell death. However, more studies are needed to clarify the role of autophagy in astrocytes exposed to the herbicide and which components of the formulation might be triggering the effects observed here.

中文翻译：

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基于草甘膦的除草剂会损害 C6 星形胶质瘤细胞系的能量代谢并增加自噬。


几位研究人员证明，草甘膦制剂会产生与氧化应激、谷氨酸能系统改变、乙酰胆碱酯酶活性抑制和线粒体功能障碍相关的神经毒性。然而，星形胶质细胞暴露于这种除草剂后的潜在分子机制尚不清楚。因此，本研究的目的是确定用草甘膦除草剂处理的星形胶质细胞中与能量代谢相关的酶的活性，以及​​氧化应激参数、线粒体质量、核面积和自噬。我们的结果表明，暴露于草甘膦除草剂 24 小时会降低大鼠的 (1) 细胞活力、(2) 线粒体呼吸链酶和肌酸激酶 (CK) 的活性、(3) 线粒体质量和 (4) 核面积星形胶质瘤细胞系（C6 细胞）。然而，在暴露于非细胞毒性浓度的除草剂的细胞中，非蛋白硫醇（NPSH）水平增加，但过氧化氢酶活性没有改变。低草甘膦浓度提高了自噬相关蛋白阳性细胞的含量。在暴露于相同浓度草甘膦的细胞中，核因子红细胞 2 相关因子 (Nrf2)、NAD(P)H 脱氢酶 [醌] 1 (NQO1) 和 PTEN 诱导激酶 1 (PINK1) 标记没有显着改变。发现了 NPSH 水平和自噬阳性细胞。可以想象，线粒体和CK可能是草甘膦除草剂的靶标。此外，自噬诱导和 NPSH 增加可能是避免氧化应激和细胞死亡的机制。 然而，需要更多的研究来阐明自噬在暴露于除草剂的星形胶质细胞中的作用以及制剂的哪些成分可能引发此处观察到的效果。