posted on 2021-11-29, 13:35authored byYu-ki Tanaka, Hana Usuzawa, Miyu Yoshida, Kazuhiro Kumagai, Keita Kobayashi, Satoshi Matsuyama, Takato Inoue, Akihiro Matsunaga, Mari Shimura, Jorge Ruiz Encinar, José M. Costa-Fernández, Yasunori Fukumoto, Noriyuki Suzuki, Yasumitsu Ogra
It is widely recognized that the
toxicity of mercury (Hg) is attenuated
by the simultaneous administration of selenium (Se) compounds in various
organisms. In this study, we revealed the mechanisms underlying the
antagonistic effect of sodium selenite (Na2SeO3) on inorganic Hg (Hg2+) toxicity in human hepatoma HepG2
cells. Observations by transmission electron microscopy indicated
that HgSe (tiemannite) granules of up to 100 nm in diameter were accumulated
in lysosomal-like structures in the cells. The HgSe granules were
composed of a number of HgSe nanoparticles, each measuring less than
10 nm in diameter. No accumulation of HgSe nanoparticles in lysosomes
was observed in the cells exposed to chemically synthesized HgSe nanoparticles.
This suggests that intracellular HgSe nanoparticles were biologically
generated from Na2SeO3 and Hg2+ ions
transported into the cells and were not derived from HgSe nanoparticles
formed in the extracellular fluid. Approximately 85% of biogenic HgSe
remained in the cells at 72 h post culturing, indicating that biogenic
HgSe was hardly excreted from the cells. Moreover, the cytotoxicity
of Hg2+ was ameliorated by the simultaneous exposure to
Na2SeO3 even before the formation of insoluble
HgSe nanoparticles. Our data confirmed for the first time that HepG2
cells can circumvent the toxicity of Hg2+ through the direct
interaction of Hg2+ with a reduced form of Se (selenide)
to form HgSe nanoparticles via a Hg–Se soluble complex in the
cells. Biogenic HgSe nanoparticles are considered the ultimate metabolite
in the Hg detoxification process.