Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, University of Cartagena, Cartagena, 130015, Colombia.
Ecotoxicol Environ Saf. 2020 Jan 15;187:109709. doi: 10.1016/j.ecoenv.2019.109709. Epub 2019 Oct 22.
Among the most used chemicals in the world are nonionic surfactants. One of these environmental pollutants is nonylphenol ethoxylate (NP-9), also known as Tergitol, and its degradation product, nonylphenol (NP). The objective of this work was to determine the toxicity of NP and NP-9 in Caenorhabditis elegans. Wild-type L4 larvae were exposed to different concentrations of the surfactants to measure functional endpoints. Mutant strains were employed to promote the activation of toxicity signaling pathways related to mtl-2, gst-1, gpx-4, gpx-6, sod-4, hsp-70 and hsp-4. Additionally, stress response was also assessed using a daf-16::GFP transgenic strain. The lethality was concentration dependent, with 24-h LC of 122 μM and 3215 μM for NP and NP-9, respectively. Both compounds inhibited nematode growth, although NP was more potent; and at non-lethal concentrations, nematode locomotion was reduced. The increase in the expression of tested genes was significant at 10 μM for NP-9 and 0.001 μM for NP, implying a likely role for the activation of oxidative and cellular stress, as well as metabolism pathways. With the exception of glutathione peroxidase, which has a bimodal concentration-response curve for NP, typical of endocrine disruption, the other curves for this xenobiotic in the strains evaluated were almost flat for most concentrations, until reaching 50-100 μM, where the effect peaked. NP and NP-9 induced the activation and nuclear translocation of DAF-16, suggesting that transcription of stress-response genes may be mediated by the insulin/IGF-1 signaling pathway. In contrast, NP-9 induced a concentration-dependent response for the sod-4 and hsp-4 mutants, with greater fluorescence induction than NP at similar levels. In short, NP and NP-9 affect the physiology of C. elegans and modulate gene expression related to ROS production, cellular stress and metabolism of xenobiotics.
在世界上使用最广泛的化学物质中,有非离子表面活性剂。这些环境污染物之一是壬基酚乙氧基化物(NP-9),也称为 Tergitol,及其降解产物壬基酚(NP)。这项工作的目的是确定 NP 和 NP-9 在秀丽隐杆线虫中的毒性。将 L4 期野生型幼虫暴露于不同浓度的表面活性剂中,以测量功能终点。利用突变株来促进与 mtl-2、gst-1、gpx-4、gpx-6、sod-4、hsp-70 和 hsp-4 相关的毒性信号通路的激活。此外,还使用 daf-16::GFP 转基因株评估了应激反应。致死率与浓度呈依赖性,NP 和 NP-9 的 24 小时 LC 分别为 122 μM 和 3215 μM。这两种化合物都抑制了线虫的生长,尽管 NP 的抑制作用更强;在非致死浓度下,线虫的运动能力下降。NP-9 在 10 μM 时,NP 在 0.001 μM 时,测试基因的表达显著增加,这表明氧化和细胞应激以及代谢途径的激活可能起作用。除了谷胱甘肽过氧化物酶外,NP 的曲线呈双峰浓度反应,表明其具有内分泌干扰作用,而在评估的菌株中,这种外源化学物质的其他曲线在大多数浓度下几乎呈平坦状,直到达到 50-100 μM 时,作用达到峰值。NP 和 NP-9 诱导了 DAF-16 的激活和核转位,表明应激反应基因的转录可能是由胰岛素/IGF-1 信号通路介导的。相比之下,NP-9 诱导 sod-4 和 hsp-4 突变体的浓度依赖性反应,在相似水平下,其诱导的荧光比 NP 更强。总之,NP 和 NP-9 影响秀丽隐杆线虫的生理学,并调节与 ROS 产生、细胞应激和外源化学物质代谢相关的基因表达。