HgS and Zuotai differ from HgCl2 and methyl mercury in intestinal Hg absorption, transporter expression and gut microbiome in mice

Toxicol Appl Pharmacol. 2019 Sep 15:379:114615. doi: 10.1016/j.taap.2019.114615. Epub 2019 Jun 6.

Abstract

Mercury (Hg) is generally considered as a toxic metal; yet the biological outcomes of Hg-containing compounds are highly dependent upon their chemical forms. We hypothesize that mercury sulfide (HgS) is different from HgCl2 and methylmercury (MeHg) in producing intestinal Hg absorption and disruption of gut microbiome. To test this hypothesis, mice were given orally with HgS (α-HgS, 30 mg/kg), Zuotai (β-HgS, 30 mg/kg), HgCl2 (33.6 mg/kg, equivalent Hg as HgS), or MeHg (3.1 mg/kg, 1/10 Hg as HgS) for 7 days. Accumulation of Hg in the duodenum and ileum after HgCl2 (30-40 fold) and MeHg (10-15 fold) was higher than HgS and Zuotai (~2-fold). HgCl2 and MeHg decreased intestinal intake peptide transporter-1 and Ost-β, and increased ileal bile acid binding protein and equilibrative nucleoside transporter-1. The efflux transporters ATP-binding cassette sub-family C member-4 (Abcc4), Abcg2, Abcg5/8, and Abcb1b were increased by HgCl2 and to a lesser extent by MeHg, while HgS and Zuotai had minimal effects. Bacterial DNA was extracted and subjected to 16S rDNA sequencing. Operational taxonomic unit (OTU) results showed that among the 10 phyla, HgS increased Firmicutes, Proteobacteria, while HgCl2 increased Bacteroidetes, Cyanobacteria and decreased Firmicutes; among the 79 families, HgS increased Rikenellaceae, Lactobacillaceae, Helicobacteraceae, and decreased Prevotellaceae, while HgCl2 increased Odoribacteraceae, Porphyromonadaceae, and decreased Lactobacillaceae; among the 232 genus/species, HgS and Zuotai affected gut microbiome quite differently from HgCl2 and MeHg. qPCR analysis with 16S rRNA confirmed sequencing results. Thus, chemical forms of mercury are a major determinant for intestinal Hg accumulation, alterations in transporters and disruption of microbiome.

Keywords: Gut microbiome; Gut transporter; HgCl(2); HgS; MeHg; Zuotai.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Duodenum / metabolism
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Ileum / metabolism
  • Ileum / pathology
  • Intestinal Absorption / drug effects*
  • Male
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / metabolism
  • Mercuric Chloride / toxicity*
  • Mercury Compounds / pharmacokinetics*
  • Mercury Compounds / toxicity
  • Mice
  • RNA, Ribosomal, 16S / genetics
  • Real-Time Polymerase Chain Reaction

Substances

  • Membrane Transport Proteins
  • Mercury Compounds
  • RNA, Ribosomal, 16S
  • zuotai
  • Mercuric Chloride
  • cinnabar