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氟化物在非细胞毒性浓度下对A549肺细胞系产生毒性作用。

Fluoride Induces Toxic Effects on the A549 Pulmonary Cell Line at Non-cytotoxic Concentrations.

作者信息

J E Sánchez-Gasca, Y Debray-García, I A Corona-Galvan, T M Uribe-Ramirez, M P Sierra-Vargas, O G Aztatzi-Aguilar

机构信息

Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, AvInstituto Politécnico Nacional 2508, Col San Pedro ZacatencoCDMX, C.P. 07360, Mexico City, Mexico.

Departamento de Investigación en Toxicología y Medicina Ambiental, Instituto Nacional de Enfermedades Respiratorias, CDMX, Calz. de Tlalpan 4502, Belisario Domínguez Secc 16, C.P. 14080, Mexico City, Mexico.

出版信息

Biol Trace Elem Res. 2025 Jan 4. doi: 10.1007/s12011-024-04499-5.

DOI:10.1007/s12011-024-04499-5
PMID:39753787
Abstract

Fluoride is emitted into the air not only through gas emissions but also from volcanic ash, leading to contact via inhalation. Therefore, the objective of the present study was to evaluate the cellular and biochemical responses in the A549 cell line after exposure to NaF (sodium fluoride) concentrations lower than those previously used in other studies to determine the impact on the lung epithelium. A549 cells were exposed to different concentrations (0.0001 to 5 mM) of NaF for 24 h. No cytotoxicity was observed in the cells after exposure to NaF concentrations of 0.0001 to 1 mM. However, an increase in oxidative damage was observed at concentrations of 0.0001-0.001 and 1-5 mM. There were alterations in the antioxidant system related to glutathione synthesis, since there was a decrease in glutathione-s-transferase activity and γ-glutamyltransferase concentration at non-cytotoxic concentrations. Non-cytotoxic concentrations also resulted in an increase in the expression of the proteins pulmonary surfactant B and γ-glutamyl cysteine ligase. A reduction in PPARα was also observed, which coincided with a decrease in the levels of non-esterified fatty acids at the same NaF concentrations. Finally, IL-6 was the only interleukin with increased levels at all NaF concentrations. In general, an increase was also observed in the other interleukins, but only at concentrations of 0.1-5 mM. These results suggest that the lung epithelium may be a toxicological target of fluoride after exposure to low concentrations.

摘要

氟化物不仅通过气体排放进入空气,还会从火山灰中释放出来,导致通过吸入接触。因此,本研究的目的是评估A549细胞系在暴露于低于其他研究中使用的氟化钠(NaF)浓度后,细胞和生化反应,以确定对肺上皮的影响。将A549细胞暴露于不同浓度(0.0001至5 mM)的NaF中24小时。在暴露于0.0001至1 mM的NaF浓度后,未观察到细胞的细胞毒性。然而,在0.0001-0.001和1-5 mM的浓度下观察到氧化损伤增加。与谷胱甘肽合成相关的抗氧化系统发生了改变,因为在非细胞毒性浓度下谷胱甘肽 - s - 转移酶活性和γ - 谷氨酰转移酶浓度降低。非细胞毒性浓度还导致肺表面活性物质B和γ - 谷氨酰半胱氨酸连接酶蛋白的表达增加。还观察到PPARα的减少,这与相同NaF浓度下非酯化脂肪酸水平的降低一致。最后,IL - 6是在所有NaF浓度下水平均升高的唯一白细胞介素。一般来说,在其他白细胞介素中也观察到增加,但仅在0.1 - 5 mM的浓度下。这些结果表明,低浓度暴露后,肺上皮可能是氟化物的毒理学靶点。

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本文引用的文献

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Pattern Recognition of Trace Element vs Heavy Elements in Patients with Membranous Nephropathy.膜性肾病患者微量元素与重金属元素的模式识别
Biol Trace Elem Res. 2024 Nov 30. doi: 10.1007/s12011-024-04461-5.
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Toxicity of fluoride: critical evaluation of evidence for human developmental neurotoxicity in epidemiological studies, animal experiments and in vitro analyses.氟化物的毒性:流行病学研究、动物实验和体外分析中人类发育神经毒性证据的批判性评估。
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氟化物毒性及其细胞反应的原理:综述。
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Osteoprotegerin and osteopontin levels, but not gene polymorphisms, predict mortality in cardiovascular diseases.骨保护素和骨桥蛋白水平,但不是基因多态性,可预测心血管疾病的死亡率。
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Chronic fluorosis: The disease and its anaesthetic implications.慢性氟中毒:疾病及其麻醉学影响
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7
Effects of sodium fluoride on immune response in murine macrophages.氟化钠对小鼠巨噬细胞免疫反应的影响。
Toxicol In Vitro. 2016 Aug;34:81-87. doi: 10.1016/j.tiv.2016.03.001. Epub 2016 Mar 7.
8
Tamarind seed coat ameliorates fluoride induced cytotoxicity, oxidative stress, mitochondrial dysfunction and apoptosis in A549 cells.罗望子种皮改善了 A549 细胞中氟诱导的细胞毒性、氧化应激、线粒体功能障碍和细胞凋亡。
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9
Sodium fluoride affects zebrafish behaviour and alters mRNA expressions of biomarker genes in the brain: Role of Nrf2/Keap1.氟化钠影响斑马鱼行为并改变大脑中生物标志物基因的mRNA表达:Nrf2/Keap1的作用。
Environ Toxicol Pharmacol. 2015 Sep;40(2):352-9. doi: 10.1016/j.etap.2015.07.003. Epub 2015 Jul 14.
10
Induction of oxidative stress and related transcriptional effects of sodium fluoride in female zebrafish liver.氟化钠诱导雌性斑马鱼肝脏氧化应激及相关转录效应。
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