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首页> 外文期刊>Journal of applied toxicology >Carbofuran cytotoxicity, DNA damage, oxidative stress, and cell death in human umbilical vein endothelial cells: Evidence of vascular toxicity
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Carbofuran cytotoxicity, DNA damage, oxidative stress, and cell death in human umbilical vein endothelial cells: Evidence of vascular toxicity

机译：人脐静脉内皮细胞中的Carbofuran细胞毒性，DNA损伤，氧化应激和细胞死亡：血管毒性的证据

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摘要

Carbofuran is a broad-spectrum carbamate insecticide, which principally inhibits the acetylcholinesterase (AChE) enzyme in the nervous system. Nonetheless, their selective action is not restricted to a single species and expanded to humans. No studies are available on the toxicological effects of carbofuran in the endothelial cells (ECs), which first confronts the toxicants in blood vessels. Hence, we have exposed the human umbilical vein ECs (HUVECs) with carbofuran for 24 h, which significantly reduced the cell survival to 25.16% and 33.48% at 500 and 1,000 mu M analyzed by MTT assay. In the neutral red uptake (NRU) assay, 16.68%, 30.99%, and 58.11% survival decline was found at 250, 500, and 1,000 mu M of carbofuran. HUVECs exposed to carbofuran showed significant increase in the intracellular reactive oxygen species (ROS), indicating oxidative stress at low concentrations. In parallel, HUVECs showed hyperpolarization effects in the mitochondrial membrane potential (Delta psi m) upon carbofuran exposure. Carbofuran induced DNA damage in HUVECs measured as 8.80, 11.82, 35.56, and 79.69 Olive tail moment (OTM) in 100-, 250-, 500-, and 1,000-mu M exposure groups. Flow cytometric analysis showed apoptotic peak (SubG1) and G2M arrest in the HUVECs exposed to carbofuran. Overall, our novel data confirm that carbofuran is toxic for the EC cells, especially at the higher concentrations, which may affect the vascular functions and possibly angiogenesis. Hence, carbofuran should be applied judiciously, and detailed vascular studies are warranted to gain an in-depth information focusing the transcriptomic and translation changes employing suitable in vivo and in vitro test models.
机译：呋喃丹是一种广谱氨基甲酸酯类杀虫剂，主要抑制神经系统中的乙酰胆碱酯酶（AChE）。尽管如此，它们的选择性行动并不局限于一个物种，而是扩展到人类。目前尚无关于呋喃丹在内皮细胞（ECs）中的毒理学效应的研究，内皮细胞首先在血管中对抗毒物。因此，我们将人脐静脉内皮细胞（HUVECs）与呋喃丹接触24小时，通过MTT分析，在500和1000μM时，细胞存活率显著降低至25.16%和33.48%。在中性红摄取（NRU）试验中，在250、500和1000μM的克百威中发现16.68%、30.99%和58.11%的存活率下降。暴露于呋喃丹的人脐静脉内皮细胞的细胞内活性氧（ROS）显著增加，表明在低浓度下存在氧化应激。同时，暴露于呋喃丹后，HUVECs在线粒体膜电位（δpsi m）中表现出超极化效应。在100、250、500和1000μM暴露组中，呋喃丹诱导的HUVEC DNA损伤分别为8.80、11.82、35.56和79.69橄榄尾矩（OTM）。流式细胞术分析显示，暴露于呋喃丹的HUVEC出现凋亡峰（SubG1）和G2M阻滞。总的来说，我们的新数据证实，呋喃丹对EC细胞有毒，尤其是在较高浓度下，这可能会影响血管功能，并可能影响血管生成。因此，应明智地使用呋喃丹，并应进行详细的血管研究，以获得更深入的信息，重点关注转录组学和翻译变化，采用合适的体内和体外试验模型。

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