Potentiation of methylmercury toxicity by combined metal exposure: in vitro and in vivo models of a restricted metal exposome
Potentiation of methylmercury toxicity by combined metal exposure: in vitro and in vivo models of a restricted metal exposome
复制标题
组合金属暴露增强甲基汞毒性：受限金属暴露组的体外和体内模型
DOI：
10.1016/j.chemosphere.2022.134374
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发表时间：
2022
期刊：
影响因子：
8.8
通讯作者：
Kumagai Y.
中科院分区：
文献类型：
--
作者：
Akiyama M.;Shinkai Y.;Yamakawa H.;Kim Y.G.;Kumagai Y.
甲基汞（MeHg）是一种普遍存在的有毒金属，很容易改变蛋白质硫醇。在氧化还原稳态中起作用的活性过硫化物能够通过硫加合物的形成使这种金属失活。尽管人类每天都接触到可消耗活性过硫化物的其他金属，但甲基汞和其他金属联合接触对健康的影响仍未得到探索。本研究旨在研究甲基汞与其他能够消耗活性过硫化物的金属一起暴露于甲基汞时的潜在毒性。我们设计了一个简单的系统来评估基于对活性过硫化物和汞积累的反应性的金属联合暴露的风险。在无电池系统中检测的金属中，铜、镉、镍和甲基汞消耗了Na2S2，这被用作活性过硫化物的模型，而锌、铁、锂、锶、锡和铝则没有。在HepG2细胞中，双重暴露于甲基汞和铜，而不是铝，增加了细胞外活性过硫化物的消耗。二重暴露通过促进甲基汞对细胞内蛋白的修饰而加重了甲基汞诱导的细胞毒性。在小鼠模型中，甲基汞和铜的双重暴露导致怀孕小鼠的胎儿和胎盘以及未怀孕小鼠的大脑和肝脏中的汞积累升高。我们的研究表明，MeHg的敏感性可以通过与其他亲电金属的联合暴露而增加。特别是，在怀孕期间，甲基汞和铜的双重暴露加剧了后代的汞积累。
Methylmercury (MeHg) is a prevalent toxic metal that readily modifies protein thiols. Reactive persulfides that play a role in redox homeostasis are able to inactivate this metal through sulfur adduct formation. Although humans are exposed to other metals that could consume reactive persulfides on a daily basis, the health effects of combined exposure to MeHg and other metals remain unexplored. This study aimed to examine potential MeHg toxicity during exposure to MeHg with other metals capable of consuming reactive persulfides. We designed a simple system to assess the risk of combined exposure to metals based on reactivity to reactive persulfides and mercury accumulation. Among the metals examined in a cell-free system, copper, cadmium, nickel, and MeHg consumed Na2S2, used as a model of reactive persulfides, whereas zinc, iron, lithium, strontium, tin, and aluminum did not. In HepG2 cells, binary exposure to MeHg and copper, but not aluminum, increased the consumption of extracellular reactive persulfides. Binary exposure exacerbated MeHg-induced cytotoxicity by promoting the modification of intracellular proteins by MeHg. In a mouse model, binary exposure to MeHg and copper resulted in elevated mercury accumulation in the fetuses and placenta of pregnant mice, as well as the brain and liver of non-pregnant mice. Our study suggests that MeHg sensitivity can be increased by combined exposure with other electrophilic metals. In particular, binary exposure to MeHg and copper during pregnancy exacerbated mercury accumulation in offspring.