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接触甲氨基阿维菌素苯甲酸盐对人 Molt-4 T 细胞具有细胞毒性作用,维生素 E 和二硫苏糖醇可能具有改善作用。

Exposure to emamectin benzoate confers cytotoxic effects on human molt-4 T-cells and possible ameliorative role of vitamin E and dithiothreitol.

机构信息

Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai, China.

出版信息

Drug Chem Toxicol. 2023 May;46(3):413-422. doi: 10.1080/01480545.2022.2044350. Epub 2022 Mar 10.

DOI:10.1080/01480545.2022.2044350
PMID:35266429
Abstract

Emamectin benzoate (EMB) is an avermectin insecticide that is extensively used for pest control, but there are few reports concerning its cytotoxic effects on human lymphocytes. In the current study, the hematotoxicity of EMB was evaluated in Molt-4 T-cells, a human T-lymphoblastic cell line with high motility, and the role of vitamin E (VitE) and dithiothreitol (DTT) in attenuating EMB cytotoxicity was characterized. Exposure of Molt-4 cells to EMB decreased cell viability and proliferation, induced a loss of cell clusters, and significantly increased membrane collapse and chromatin condensation. Moreover, EMB significantly increased cell death and suppressed transglutaminase activity. EMB treatment modulated the NF-κB signaling pathway, decreased the expression of p105, p50, and p65/RelA in cytosolic and nuclear fractions, and increased nuclear IκBα expression. EMB increased oxidative stress, as demonstrated by a significant increase in the levels of reactive oxygen species (ROS). Treatment with non-cytotoxic concentrations of VitE or DTT ameliorated the hematotoxicity induced by pretreatment with EMB, increased Molt-4 cell viability, raised the IC values of EMB, limited intracellular ROS generation, and mitigated EMB-mediated effects on NF-κB signaling. The results indicate the potential cytotoxicity of EMB on human lymphocytes, and demonstrate that VitE and DTT treatment can reduce the cytotoxic effects of EMB.

摘要

苯甲酸盐(EMB)是一种阿维菌素杀虫剂,广泛用于害虫防治,但关于其对人淋巴细胞的细胞毒性作用的报道很少。在本研究中,评估了 EMB 对高迁移性的人 T 淋巴细胞白血病细胞系 Molt-4 T 细胞的血液毒性,并且表征了维生素 E(VitE)和二硫苏糖醇(DTT)在减轻 EMB 细胞毒性中的作用。暴露于 EMB 的 Molt-4 细胞降低了细胞活力和增殖,导致细胞簇丧失,并且显著增加了膜崩溃和染色质凝聚。此外,EMB 显著增加细胞死亡并抑制转谷氨酰胺酶活性。EMB 处理调节 NF-κB 信号通路,降低细胞质和核部分中 p105、p50 和 p65/RelA 的表达,并增加核 IκBα 的表达。EMB 增加氧化应激,如活性氧(ROS)水平的显著增加所证明。用非细胞毒性浓度的 VitE 或 DTT 预处理可减轻 EMB 引起的血液毒性,增加 Molt-4 细胞活力,提高 EMB 的 IC 值,限制细胞内 ROS 的产生,并减轻 EMB 对 NF-κB 信号的介导作用。结果表明 EMB 对人淋巴细胞具有潜在的细胞毒性,并且表明 VitE 和 DTT 处理可以降低 EMB 的细胞毒性作用。

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