In vitro toxicological characterization of two arsenosugars and their metabolites.
In vitro toxicological characterization of two arsenosugars and their metabolites.
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DOI：
10.1002/mnfr.201200821
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发表时间：
2013-07
影响因子：
5.2
通讯作者：
Schwerdtle, Tanja
中科院分区：
文献类型：
--
作者：
Leffers, Larissa;Ebert, Franziska;Taleshi, Mojtaba S.;Francesconi, Kevin A.;Schwerdtle, Tanja
欧洲食品安全局在最近发表的《关于食品中砷的科学意见》中得出结论，目前不可能对砷糖进行风险评估，主要是因为缺乏相关的毒理学数据。为了解决这个问题，我们进行了毒理学体外表征的两个砷糖和六砷糖代谢产物。本研究中研究的高纯度合成砷糖（DMAV-糖-甘油和DMAV-糖-硫酸盐）以及四种代谢产物（氧代-二甲基砷乙酸（氧代-DMAAV）、氧代-二甲基砷乙醇（氧代-DMAEV）、硫代-DMAAV和硫代-DMAEV）在培养的人膀胱细胞中暴露至500 μM时既不产生细胞毒性也不产生遗传毒性。然而，两种砷糖代谢产物，即二甲基胂酸（DMAV）和硫代二甲基胂酸（硫代DMAV），对细胞有毒性;硫代DMAV甚至比亚砷酸盐的细胞毒性略强。此外，砷糖的肠道生物利用度采用Caco-2肠道屏障模型进行评估。所观察到的砷糖穿过屏障模型的低但显著的转移速率提供了砷糖具有体内生物可利用性的进一步证据。在代谢砷糖的细胞系统中，可能会产生细胞毒性。因此，与砷甜菜碱形成强烈对比的是，砷糖不能被归类为对人类无毒，并且不能排除对人类健康的风险。
In their recently published Scientific Opinion on Arsenic in Food, the European Food Safety Authority concluded that a risk assessment for arsenosugars is currently not possible, largely because of the lack of relevant toxicological data. To address this issue, we carried out a toxicological in vitro characterization of two arsenosugars and six arsenosugar metabolites. The highly pure synthesized arsenosugars, DMAV-sugar-glycerol and DMAV-sugar-sulfate, investigated in this study, as well as four metabolites, oxo-dimethylarsenoacetic acid (oxo-DMAAV), oxo-dimethylarsenoethanol (oxo-DMAEV), thio-DMAAV and thio-DMAEV, exerted neither cytotoxicity nor genotoxicity up to 500 μM exposure in cultured human bladder cells. However, two arsenosugar metabolites, namely dimethyl-arsinic acid (DMAV) and thio-dimethylarsinic acid (thio-DMAV), were toxic to the cells; thio-DMAV was even slightly more cytotoxic than arsenite. Additionally, intestinal bioavailability of the arsenosugars was assessed applying the Caco-2 intestinal barrier model. The observed low, but significant transfer rates of the arsenosugars across the barrier model provide further evidence that arsenosugars are intestinally bioavailable. In a cellular system that metabolizes arsenosugars, cellular toxicity likely arises. Thus, in strong contrast to arsenobetaine, arsenosugars cannot be categorized as nontoxic for humans and a risk to human health cannot be excluded.
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影响因子：
4.2
作者：
Conklin, SD;Ackerman, AH;Thomas, DJ
通讯作者：
Thomas, DJ
影响因子：
6.1
作者：
Almela, C;Laparra, JM;Montoro, R
通讯作者：
Montoro, R
影响因子：
3.3
作者：
通讯作者：
--
影响因子：
4.1
作者：
Calatayud, M.;Velez, D.;Devesa, V.
通讯作者：
Devesa, V.
DOI：
10.1007/bf01964067
发表时间：
1982-01-01
期刊：
EXPERIENTIA
影响因子：
--
作者：
EDMONDS, JS;FRANCESCONI, KA;HANSEN, JA
通讯作者：
HANSEN, JA