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砷会改变环境暴露儿童单核细胞超氧阴离子和一氧化氮的产生。

Arsenic alters monocyte superoxide anion and nitric oxide production in environmentally exposed children.

机构信息

Toxicologia, Cinvestav, PO Box: 14-740, Mexico, D.F., 07360, Mexico.

出版信息

Toxicol Appl Pharmacol. 2010 Jun 1;245(2):244-51. doi: 10.1016/j.taap.2010.03.006. Epub 2010 Mar 11.

Abstract

Arsenic (As) exposure has been associated with alterations in the immune system, studies in experimental models and adults have shown that these effects involve macrophage function; however, limited information is available on what type of effects could be induced in children. The aim of this study was to evaluate effects of As exposure, through the association of inorganic As (iAs) and its metabolites [monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] with basal levels of nitric oxide (NO(-)) and superoxide anion (O(2)(-)), in peripheral blood mononuclear cells (PBMC) and monocytes, and NO(-) and O(2)(-) produced by activated monocytes. Hence, a cross-sectional study was conducted in 87 children (6-10 years old) who had been environmentally exposed to As through drinking water. Levels of urinary As species (iAs, MMA and DMA) were determined by hydride generation atomic absorption spectrometry, total As (tAs) represents the sum of iAs and its species; tAs urine levels ranged from 12.3 to 1411 microg/g creatinine. Using multiple linear regression models, iAs presented a positive and statistical association with basal NO(-) in PBMC (beta=0.0048, p=0.049) and monocytes (beta=0.0044, p=0.044), while basal O(2)(-) had a significant positive association with DMA (beta=0.0025, p=0.046). In activated monocytes, O(2)(-) showed a statistical and positive association with iAs (beta=0.0108, p=0.023), MMA (beta=0.0066, p=0.022), DMA (beta=0.0018, p=0.015), and tAs (beta=0.0013, p=0.015). We conclude that As exposure in the studied children was positively associated with basal levels of NO(-) and O(2)(-) in PBMC and monocytes, suggesting that As induces oxidative stress in circulating blood cells. Additionally, this study showed a positive association of O(2)(-) production with iAs and its metabolites in stimulated monocytes, supporting previous data that suggests that these cells, and particularly the O(2)(-) activation pathway, are relevant targets for As toxicity.

摘要

砷(As)暴露与免疫系统的改变有关,实验模型和成年人的研究表明,这些影响涉及巨噬细胞功能;然而,关于儿童可能产生的影响,信息有限。本研究旨在通过评估无机砷(iAs)及其代谢物[一甲基砷(MMA)和二甲基砷(DMA)]与外周血单个核细胞(PBMC)和单核细胞中一氧化氮(NO(-))和超氧阴离子(O(2)(-))的基础水平之间的关联,来评估砷暴露的影响,以及激活的单核细胞中产生的 NO(-)和 O(2)(-)。因此,对 87 名儿童(6-10 岁)进行了一项横断面研究,这些儿童通过饮用水环境暴露于砷。采用氢化物发生原子吸收光谱法测定尿砷种类(iAs、MMA 和 DMA),总砷(tAs)表示 iAs 及其种类的总和;tAs 尿水平范围为 12.3 至 1411 微克/克肌酐。使用多元线性回归模型,iAs 与 PBMC(β=0.0048,p=0.049)和单核细胞(β=0.0044,p=0.044)中基础 NO(-)呈正相关和统计学关联,而基础 O(2)(-)与 DMA 呈显著正相关(β=0.0025,p=0.046)。在激活的单核细胞中,O(2)(-)与 iAs(β=0.0108,p=0.023)、MMA(β=0.0066,p=0.022)、DMA(β=0.0018,p=0.015)和 tAs(β=0.0013,p=0.015)呈统计学和正相关。我们得出结论,在所研究的儿童中,砷暴露与 PBMC 和单核细胞中基础水平的 NO(-)和 O(2)(-)呈正相关,表明砷诱导循环血细胞中的氧化应激。此外,本研究显示 O(2)(-)产生与刺激单核细胞中的 iAs 及其代谢物呈正相关,这支持了先前的数据,表明这些细胞,特别是 O(2)(-)激活途径,是砷毒性的相关靶标。

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