Institute of Environmental Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Hematology-Oncology Section, LANDSEED Hospital, Jhongli, Taiwan.
Ecotoxicol Environ Saf. 2019 May 15;172:432-438. doi: 10.1016/j.ecoenv.2019.01.036. Epub 2019 Feb 6.
Diuron is an herbicide, which is used to control a wide variety of annual and perennial broadleaf, grassy weeds, and mosses. However, the toxicity of diuron in HepG2 cells and zebrafish embryos was unclear. In this study, HpeG2 cells and zebrafish embryos were exposed to different concentrations of diuron for 24 h and 48 h, respectively. Results reveal the diuron caused cytotoxicity and the generation of reactive oxygen species (ROS) in the treated HepG2 cells. The effects of diuron on the expression of catalase and superoxide dismutase (SOD1 and SOD2), an antioxidant enzyme, were investigated. Results showed that only SOD1 was significantly induced after treated diuron 48 h, but the expression of catalase and SOD2 was unaffected. Additionally, the cytotoxicity of diuron was not attenuated in cells pretreated with of N-acetyl-cysteine (NAC), a well-known antioxidant, indicating that oxidative stress could not contribute to cellular death in the treated HepG2 cells. In zebrafish embryos, results from proteomic analysis show that 332 differentially upregulated proteins and 199 down-regulated proteins were detected in the treated embryos (P < 0.05). In addition to the up-regulated antioxidant proteins (prdx3, cat, prdx4, txnrd1, prdx1, sod1, prdx2, and sod2), some decreased proteins were related to cytoskeleton formation, tight junction, and gap junction, which could be related to the malformation of the treated zebrafish embryos. In summary, diuron caused cytotoxicity in HepG2 cells, and the mechanisms of toxicity in zebrafish were addressed using the proteomic analysis.
敌草隆是一种除草剂，用于控制多种一年生和多年生阔叶杂草、草和苔藓。然而，敌草隆对 HepG2 细胞和斑马鱼胚胎的毒性尚不清楚。在这项研究中，分别用不同浓度的敌草隆处理 HepG2 细胞和斑马鱼胚胎 24 和 48 小时。结果表明，敌草隆在处理的 HepG2 细胞中引起细胞毒性和活性氧（ROS）的产生。研究了敌草隆对过氧化氢酶和超氧化物歧化酶（SOD1 和 SOD2）等抗氧化酶表达的影响。结果表明，仅在处理敌草隆 48 小时后 SOD1 的表达显著增加，但过氧化氢酶和 SOD2 的表达不受影响。此外，在用 N-乙酰半胱氨酸（NAC）预处理的细胞中，敌草隆的细胞毒性没有减弱，NAC 是一种众所周知的抗氧化剂，表明氧化应激不能导致处理的 HepG2 细胞中的细胞死亡。在斑马鱼胚胎中，蛋白质组学分析的结果表明，处理后的胚胎中检测到 332 个上调蛋白和 199 个下调蛋白（P<0.05）。除了上调的抗氧化蛋白（prdx3、cat、prdx4、txnrd1、prdx1、sod1、prdx2 和 sod2）外，一些下调蛋白与细胞骨架形成、紧密连接和间隙连接有关，这可能与处理后的斑马鱼胚胎畸形有关。总之，敌草隆在 HepG2 细胞中引起细胞毒性，并通过蛋白质组学分析研究了其在斑马鱼中的毒性机制。
