Toxicological effects of Sb(III), Sb(V), and NMG-Sb(V) in human lung, kidney, and liver cells: cytotoxicity and fibrotic factor induction.

IF 1.8 4区 医学 Q4 TOXICOLOGY
Nicole Roldán, Marcelo Verdugo, Noriyuki Suzuki, Natali Zamora, Waldo Quiroz, Alexis Gonzalez, Javier Tognarelli, Yasumitsu Ogra
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引用次数: 0

Abstract

Antimony ecotoxicity studies are often hindered by the incorrect selection of Sb(III) standards and the application of concentrations that do not reflect real environmental exposure. In this study, we used environmentally relevant concentrations of inorganic Sb in its pentavalent [Sb(V)] and trivalent [Sb(III)] oxidation states, as well as the organic species NMG-Sb(V), which is present in Meglumine Antimoniate, to evaluate the effects of Sb on cell viability in human lung (A549), kidney (HEK293), and liver (HepG2) cell lines. Cell viability was assessed in these cells following treatment with 0.001 to 1 µg/L of Sb(V), 1 to 500 µg/L of Sb(III), and 0 to 1000 mg/L of MA. We also measured ROS production and the expression of the profibrotic markers CTGF, α-SMA, and PAI-1, which are associated with fibrosis activation. No significant changes in cell viability were observed in HepG2 and A549 cells. However, in HEK293 cells, viability decreased by 20-40% at Sb(III) concentrations between 1 µg/L and 1 mg/L. CTGF expression was significantly increased at 17 µg/L of Sb(III), while α-SMA and PAI-1 expression increased at 21 µg/L of Sb(V). These findings suggest that different species of Sb can induce increased expression of mRNA for fibrotic genes in human liver and kidney cell lines at concentrations found in the environment.

Sb(III)、Sb(V)和NMG-Sb(V)在人肺、肾和肝细胞中的毒理学效应:细胞毒性和纤维化因子诱导。
锑的生态毒性研究经常受到不正确的锑(III)标准选择和不反映实际环境暴露浓度的应用的阻碍。在这项研究中,我们使用环境相关浓度的无机Sb在其五价[Sb(V)]和三价[Sb(III)]氧化态,以及有机物种NMG-Sb(V),它存在于锑酸Meglumine中,来评估Sb对人肺(A549)、肾(HEK293)和肝(HepG2)细胞系细胞活力的影响。在用0.001至1µg/L Sb(V)、1至500µg/L Sb(III)和0至1000 mg/L MA处理这些细胞后,评估细胞活力。我们还测量了ROS的产生以及与纤维化激活相关的促纤维化标志物CTGF、α-SMA和PAI-1的表达。HepG2和A549细胞活力未见明显变化。然而,在HEK293细胞中,Sb(III)浓度在1µg/L和1 mg/L之间时,细胞活力下降了20-40%。17µg/L Sb(III)显著增加CTGF表达,21µg/L Sb(V)显著增加α-SMA和PAI-1表达。这些结果表明,不同种类的Sb在环境浓度下可以诱导人肝脏和肾脏细胞系中纤维化基因mRNA的表达增加。
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来源期刊
CiteScore
3.20
自引率
5.00%
发文量
53
审稿时长
4-8 weeks
期刊介绍: The Journal of Toxicological Sciences (J. Toxicol. Sci.) is a scientific journal that publishes research about the mechanisms and significance of the toxicity of substances, such as drugs, food additives, food contaminants and environmental pollutants. Papers on the toxicities and effects of extracts and mixtures containing unidentified compounds cannot be accepted as a general rule.
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