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Comparison of In Vivo with In Vitro Pharmacokinetics of Mercury Between Methylmercury Chloride and Methylmercury Cysteine Using Rats and Caco2 Cells

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Abstract

The in vivo and in vitro pharmacokinetics of mercury (Hg) were compared between methylmercury chloride (MeHg·Cl) and methylmercury cysteine (MeHg-Cys) using rats and Caco2 cells because humans can be exposed to MeHg compounds through dietary fish. The in vivo pharmacokinetics of Hg immediately after the digestion of MeHg compounds are still obscure. In Caco2 cells, membrane uptake and subcellular distribution of MeHg compounds were examined. When rats received it intravenously, MeHg·Cl showed 20-fold greater plasma and 2-fold greater blood concentrations of Hg than MeHg-Cys, indicating that their pharmacokinetic properties are different. One hour later, however, Hg concentrations in plasma and blood became virtually identical between MeHg·Cl and MeHg-Cys, although blood Hg concentrations were >100-fold greater than those in plasma. When administered into the closed rat’s jejunum loop, MeHg·Cl and MeHg-Cys were rapidly and efficiently taken up by intestinal membranes, and Hg was retained in intestinal membranes for a relatively long time. When administered orally, no difference was observed in plasma and blood Hg concentrations between MeHg·Cl and MeHg-Cys: plasma and blood Hg concentrations increased gradually and reached steady levels at 8 h after administration. In Caco2 cells, uptake of MeHg-Cys was significantly suppressed by l-leucine, although this was not seen with MeHg·Cl. In Caco2 cells, 81 % of Hg was recovered from cytosol fractions and 13 % of Hg from nuclear fractions (including debris) after a 2-h incubation with MeHg-Cys. In conclusion, the mechanism of membrane uptake and volume of distribution in the initial distribution phase were clearly different between MeHg·Cl and MeHg-Cys. However, such pharmacokinetic differences between them disappeared 1 h after intravenous and after oral routes of administration, possibly due to the metabolism in the body.

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Authors and Affiliations

  1. Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hiro-koshingai, Kure, Hiroshima, 737-0112, Japan

    Nobuhiro Mori, Eri Tsukada, Tomoharu Yokooji & Teruo Murakami

  2. Department of Basic Medical Sciences, National Institute for Minamata Disease, 4058-18 Hama, Kumamoto, Minamata City, 867-0008, Japan

    Megumi Yamamoto, Naoko Matsumura & Masanori Sasaki

Authors
  1. Nobuhiro Mori
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  2. Megumi Yamamoto
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  3. Eri Tsukada
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  4. Tomoharu Yokooji
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  5. Naoko Matsumura
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  6. Masanori Sasaki
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  7. Teruo Murakami
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Correspondence to Teruo Murakami.

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Mori, N., Yamamoto, M., Tsukada, E. et al. Comparison of In Vivo with In Vitro Pharmacokinetics of Mercury Between Methylmercury Chloride and Methylmercury Cysteine Using Rats and Caco2 Cells. Arch Environ Contam Toxicol 63, 628–636 (2012). https://doi.org/10.1007/s00244-012-9800-5

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  • DOI: https://doi.org/10.1007/s00244-012-9800-5

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