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不同器官来源的人细胞系中蓖麻毒素的差异毒性。

Differential toxicity of abrin in human cell lines of different organ origin.

机构信息

Division of Pharmacology & Toxicology, Defence Research Development & Establishment, Defence Research Development Organization, Gwalior 474002, India.

Division of Pharmacology & Toxicology, Defence Research Development & Establishment, Defence Research Development Organization, Gwalior 474002, India.

出版信息

Toxicol In Vitro. 2022 Feb;78:105250. doi: 10.1016/j.tiv.2021.105250. Epub 2021 Sep 30.

Abstract

Abrus precatorius is a highly toxic seed containing the poison abrin. Similar in properties to ricin, this toxin binds to ribosomes causing cessation of protein synthesis and cell death. With an estimated human lethal dose of 0.1-1 μg/kg, it has been the cause of fatalities due to accidental and intentional ingestion. In present study, we profiled seven human cell lines of different organ origin, for their sensitivity against abrin toxicity. These cell lines are, A549, COLO 205, HEK 293, HeLa, Hep G2, Jurkat, SH-SY5Y and derived from lung, intestine, kidney, cervix, liver, immune and nervous system respectively. MTT, NR, CVDE and LDH assays have been used to determine their response against abrin toxin. Among these cell lines A549 was the most sensitive cell line while Hep G2 was found least sensitive cell lines. Hep G2 cells are shown to have mitochondrial resistance and delayed generation of oxidative stress compared to A549 cells. Remarkable variation in sensitivity against abrin toxicity prompted the evaluation of Bcl2, Bax and downstream caspases in both cells. Difference in Bcl2 level has been shown to play important role in variable sensitivity. Findings of present study are helpful for selection of suitable cellular model for toxicity assessment and antidote screening.

摘要

相思豆是一种含有相思豆毒素的剧毒种子。这种毒素的性质与蓖麻毒素相似,与核糖体结合会导致蛋白质合成停止和细胞死亡。由于意外和故意摄入,其估计人类致死剂量为 0.1-1μg/kg,已导致死亡事件。在本研究中,我们对七种不同器官来源的人类细胞系进行了分析,以评估它们对相思豆毒素的敏感性。这些细胞系分别是 A549、COLO 205、HEK 293、HeLa、Hep G2、Jurkat 和 SH-SY5Y,分别来源于肺、肠、肾、子宫颈、肝、免疫和神经系统。我们使用 MTT、NR、CVDE 和 LDH 测定法来确定它们对相思豆毒素的反应。在这些细胞系中,A549 是最敏感的细胞系,而 Hep G2 是最不敏感的细胞系。与 A549 细胞相比,Hep G2 细胞表现出对线粒体的抗性和延迟产生氧化应激。对相思豆毒素敏感性的显著差异促使我们在这两种细胞中评估 Bcl2、Bax 和下游半胱天冬酶。Bcl2 水平的差异表明在可变敏感性中起着重要作用。本研究的发现有助于选择合适的细胞模型进行毒性评估和解毒剂筛选。

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