Abstract
A previous study by our group indicated that methylmercury (MeHg) is biotransformed to bismethylmercury sulfide [(MeHg)2S)] by interaction with reactive sulfur species (RSS) produced in the body. In the present study, we explored the transformation of MeHg to (MeHg)2S in the gut and the subsequent fate of (MeHg)2S in vitro and in vivo. An ex vivo experiment suggested the possibility of the extracellular transformation of MeHg to (MeHg)2S in the distal colon, and accordingly, the MeHg sulfur adduct was detected in the intestinal contents and feces of mice administered MeHg, suggesting that (MeHg)2S is formed through reactions between MeHg and RSS in the gut. In a cell-free system, we found that (MeHg)2S undergoes degradation in a time-dependent manner, resulting in the formation of mercury sulfide and dimethylmercury (DMeHg), as determined by X-ray diffraction and gas chromatography/mass spectrometry, respectively. We also identified DMeHg in the expiration after the intraperitoneal administration of (MeHg)2S to mice. Thus, our present study identified a new fate of MeHg through (MeHg)2S as an intermediate, which leads to conversion of volatile DMeHg in the body.
Highlights
A previous study by our group indicated that methylmercury (MeHg) is biotransformed to bismethylmercury sulfide [(MeHg)2S)] by interaction with reactive sulfur species (RSS) produced in the body
We previously found that a lower MeHg dose modifies Kelch-like ECH-associated protein 1 (Keap1) and phosphatase and tensin homolog deleted on chromosome ten (PTEN), leading to the activation of the Keap1/nuclear factor E2 related factor 2 (Nrf2) pathway and PTEN/Akt signaling, which are related to detoxication of xenobiotics and cell survival, respectively, whereas MeHg at a high dose disrupts cellular homeostasis, resulting in cell death[5,6]
Some MeHg in tissues interacts with small molecular nucleophiles, such as glutathione (GSH) produced by glutamate-cysteine ligase (GCL), in the absence and presence of GSH S-transferase (GST), and these interactions are referred to as phase II reactions and result in the formation of GSH adducts, which are excreted into the extracellular space through multidrug resistance-associated protein (MRP) in phase III r eactions[9]
Summary
A previous study by our group indicated that methylmercury (MeHg) is biotransformed to bismethylmercury sulfide [(MeHg)2S)] by interaction with reactive sulfur species (RSS) produced in the body. Hydrophobic MeHg from cells (tissues) by conversion to a more hydrophilic GSH adduct (Fig. 1) because this transcription factor cooperatively regulates the gene expression of GCL, GST and M RP10,11. Subsequent examination indicated that (MeHg)2S is formed by the interaction of MeHg with reactive sulfur species (RSS), which exhibit high n ucleophilicity[17,18] and include compounds such as GSH persulfide (GSSH) and protein-bound persulfide derived from CysSH persulfide (CysSSH) and hydrogen sulfide ( H2S) produced by transsulfuration or enzymatic activities, such as cystathionine γ-lyase (CSE) a ctivity[19] (see Fig. 1). We explored (1) the biotransformation of MeHg to (MeHg)2S in the gut and (2) the fate of (MeHg)2S in vitro and in vivo
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