Potentiation of methylmercury toxicity by combined metal exposure: In vitro and in vivo models of a restricted metal exposome

Masahiro Akiyama, Yasuhiro Shinkai, Hiroto Yamakawa, Yun Gi Kim, Yoshito Kumagai

研究成果: Article査読

3 被引用数 (Scopus)


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.

出版ステータスPublished - 2022 7月

ASJC Scopus subject areas

  • 環境工学
  • 化学一般
  • 環境化学
  • 汚染
  • 公衆衛生学、環境および労働衛生
  • 健康、毒物学および変異誘発


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