许梦川^1,2,
谈勇²,
李小满²,
李前^2,,,
吴跃峰¹,
李东明^1,,
1. 河北师范大学生命科学学院 河北省动物生理生化与分子生物学重点实验室, 石家庄 050024;
2. 军事科学院军事医学研究院毒物药物研究所 抗毒药物与毒理学国家重点实验室, 北京 100850

作者简介: 许梦川(1990-),女,硕士研究生,研究方向为动物生态学,E-mail:xumengchuan@163.com.

通讯作者: 李前,bjliqian@sina.com ; 李东明,lidngmng@gmail.com

基金项目: 国家自然科学基金(31672292)；河北省自然科学基金(C2017205059)


中图分类号: X171.5

Toxicological Effects of Acute Paraquat Exposure on L-O2 Hepatocytes

Xu Mengchuan^1,2,
Tan Yong²,
Li Xiaoman²,
Li Qian^2,,,
Wu Yuefeng¹,
Li Dongming^1,,
1. Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, China;
2. State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China

Corresponding authors: Li Qian,bjliqian@sina.com ; Li Dongming,lidngmng@gmail.com

CLC number: X171.5

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摘要:百草枯(paraquat, PQ)是目前农业生产上使用较为广泛的除草剂,PQ毒性极大,能造成人和动物多器官损伤。因肝脏是主要的受损器官之一,故以肝细胞L-O2为研究对象,探讨PQ急性暴露对肝细胞产生的毒理影响。结果显示在40~640 μmol·L^-1暴露浓度下作用24 h,PQ显著抑制肝细胞L-O2的增殖活性(P<0.01),半抑制浓度(IC₅₀)为263.2 μmol·L^-1。将肝细胞L-O2暴露于不同浓度的PQ(60、120、180和250 μmol·L^-1),作用24 h后,与对照组相比,PQ暴露组的活性氧(ROS)累积和细胞凋亡率都表现出明显的浓度依赖性升高(P<0.01;P<0.05),细胞周期阻滞在S期。Western blot结果显示,除60 μmol·L^-1外的其他暴露组中活化的胱天蛋白酶9(caspase-9)表达显著上调,Bax和Bcl-2的比值显著增大,提示细胞凋亡机制可能与内源性线粒体通路的激活有关。此外,碳酸酐酶9(CA9)mRNA表达显著升高,提示PQ暴露下可能引起酸性代谢产物出现,对细胞产生酸毒害,但其内在的机制还需进一步研究。
关键词: 百草枯/
细胞,L-O2/
细胞凋亡,碳酸酐酶9

Abstract:Paraquat (PQ) is one of the most widely used herbicides, but with ultrahigh toxicity. Its toxic effect was suggested to be related to the effect of oxidation-responsive stress, leading to multi-organ dysfunctions. As liver is the most important detoxification organ, here we reported the toxicological effects of PQ on L-O2 hepatocytes when it was acutely exposed to PQ. Our results showed that PQ was highly toxic to L-O2 hepatocytes with IC₅₀ of 263.2 μmol·L^-1 for 24 h (P<0.01). When L-O2 hepatocytes were exposed to PQ of different concentrations (60, 120, 180, 250 μmol·L^-1) for 24 h, the concentration-dependent increase of ROS accumulation and apoptosis rate of L-O2 hepatocytes were observed, compared to the control group (with P<0.01, P<0.05, respectively). The cell cycle was blocked in S phase. Further mechanistic studies were conducted on the toxicity and the apoptotic pathways. The abnormal high level of the activated caspase-9 and the ratio of Bax to Bcl-2 might indicate that an endogenous mitochondrial apoptosis could be responsible for the increased apoptosis rate of L-O2, and the distinct mRNA relative expression of carbonic anhydrase 9 (CA9) indicated the acidic toxicity inside the cells, but it is necessary to study further.
Key words:paraquat/
L-O2 hepatocytes/
apoptosis.