Skip to main content

Advertisement

Log in

High accumulation of arsenic in the esophagus of mice after exposure to arsenite

  • Inorganic Compounds
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Arsenic-induced toxicity appears to be dependent on the tissue- or cell-specific accumulation of this metalloid. An early study showed that arsenic was retained in the esophagus as well as the liver, kidney cortex and skin of marmosets after intraperitoneal administration of 74As-arsenite. However, there is little available information regarding the distribution of arsenic in the esophagus. Here, we compared the retention of arsenic in the esophagus, liver, lung, kidney and heart in mice intraperitoneally administered 1 or 5 mg/kg sodium arsenite (As(III)) daily for 3 or 7 days. The results showed that the arsenic concentration was highest in the esophagus. We compared the mRNA levels of aquaglyceroporin (AQP) 3, AQP7 and AQP9, which are responsible for arsenic influx, and those of multidrug-resistance protein (MRP) 1 and MRP2, which are responsible for arsenic efflux. The levels of AQP3 mRNA in the esophagus were much higher than those in liver, lung and heart, while the mRNA levels of MRP2 were very low in the esophagus. In addition, we found extremely low expression of Nrf2 in the esophagus at the basal and under the activated conditions, which might have resulted in low levels of glutamyl-cysteine ligase catalytic and modulatory subunits, and subsequently in the low levels of glutathione. Thus, the highest retention of arsenic was detected in the esophagus after intraperitoneal administration of As(III) to mice, and this appeared to result from multiple factors, including high expression of AQP3, low expression of MRP2, low capacity of glutathione synthesis and low activation of Nrf2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Aono J, Yanagawa T, Itoh K et al (2003) Activation of Nrf2 and accumulation of ubiquitinated A170 by arsenic in osteoblasts. Biochem Biophys Res Commun 305(2):271–277

    Article  CAS  PubMed  Google Scholar 

  • Aposhian HV, Aposhian MM (2006) Arsenic toxicology: five questions. Chem Res Toxicol 19(1):1–15

    Article  CAS  PubMed  Google Scholar 

  • Bertolero F, Marafante E, Rade JE, Pietra R, Sabbioni E (1981) Biotransformation and intracellular binding of arsenic in tissues of rabbits after intraperitoneal administration of 74As labelled arsenite. Toxicology 20(1):35–44

    Article  CAS  PubMed  Google Scholar 

  • Chen CJ, Hsueh YM, Lai MS et al (1995) Increased prevalence of hypertension and long-term arsenic exposure. Hypertension 25(1):53–60

    Article  PubMed  Google Scholar 

  • Crecelius EA (1977) Changes in the chemical speciation of arsenic following ingestion by man. Environ Health Perspect 19:147–150

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hayakawa T, Kobayashi Y, Cui X, Hirano S (2005) A new metabolic pathway of arsenite: arsenic–glutathione complexes are substrates for human arsenic methyltransferase Cyt19. Arch Toxicol 79(4):183–191

    Article  CAS  PubMed  Google Scholar 

  • Healy SM, Wildfang E, Zakharyan RA, Aposhian HV (1999) Diversity of inorganic arsenite biotransformation. Biol Trace Elem Res 68(3):249–266

    Article  CAS  PubMed  Google Scholar 

  • IARC monographs on the evaluation of carcinogenic risks to humans (2012) Arsenic and Arsenic compounds. Arsenic, metals, fibres, and dusts: a review of human carcinogens, vol 100C, pp 41–85

  • Ishibashi K, Sasaki S, Fushimi K et al (1994) Molecular cloning and expression of a member of the aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells. Proc Natl Acad Sci U S A 91(14):6269–6273

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Itoh K, Chiba T, Takahashi S et al (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236(2):313–322

    Article  CAS  PubMed  Google Scholar 

  • Itoh K, Tong KI, Yamamoto M (2004) Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic Biol Med 36(10):1208–1213

    Article  CAS  PubMed  Google Scholar 

  • Kadono T, Inaoka T, Murayama N et al (2002) Skin manifestations of arsenicosis in two villages in Bangladesh. Int J Dermatol 41(12):841–846

    Article  PubMed  Google Scholar 

  • Kala SV, Neely MW, Kala G et al (2000) The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic. J Biol Chem 275(43):33404–33408

    Article  CAS  PubMed  Google Scholar 

  • Kimura A, Ishida Y, Wada T, Yokoyama H, Mukaida N, Kondo T (2005) MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice. Toxicol Appl Pharmacol 203(1):53–61

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi M, Li L, Iwamoto N et al (2009) The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Mol Cell Biol 29(2):493–502

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Koyama Y, Yamamoto T, Tani T et al (1999) Expression and localization of aquaporins in rat gastrointestinal tract. Am J Physiol 276(3 Pt 1):C621–C627

    CAS  PubMed  Google Scholar 

  • Kumagai Y, Sumi D (2007) Arsenic: signal transduction, transcription factor, and biotransformation involved in cellular response and toxicity. Annu Rev Pharmacol Toxicol 47:243–262

    Article  CAS  PubMed  Google Scholar 

  • Lee TC, Ho IC, Lu WJ, Huang JD (2006) Enhanced expression of multidrug resistance-associated protein 2 and reduced expression of aquaglyceroporin 3 in an arsenic-resistant human cell line. J Biol Chem 281(27):18401–18407

    Article  CAS  PubMed  Google Scholar 

  • Leslie EM (2012) Arsenic-glutathione conjugate transport by the human multidrug resistance proteins (MRPs/ABCCs). J Inorg Biochem 108:141–149

    Article  CAS  PubMed  Google Scholar 

  • Leslie EM, Haimeur A, Waalkes MP (2004) Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Evidence that a tri-glutathione conjugate is required. J Biol Chem 279(31):32700–32708

    Article  CAS  PubMed  Google Scholar 

  • Lin S, Shi Q, Nix FB et al (2002) A novel S-adenosyl-l-methionine: arsenic(III) methyltransferase from rat liver cytosol. J Biol Chem 277(13):10795–10803

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Shen J, Carbrey JM, Mukhopadhyay R, Agre P, Rosen BP (2002) Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9. Proc Natl Acad Sci U S A 99(9):6053–6058

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu Z, Carbrey JM, Agre P, Rosen BP (2004) Arsenic trioxide uptake by human and rat aquaglyceroporins. Biochem Biophys Res Commun 316(4):1178–1185

    Article  CAS  PubMed  Google Scholar 

  • Lorico A, Bertola A, Baum C, Fodstad O, Rappa G (2002) Role of the multidrug resistance protein 1 in protection from heavy metal oxyanions: investigations in vitro and in MRP1-deficient mice. Biochem Biophys Res Commun 291(3):617–622

    Article  CAS  PubMed  Google Scholar 

  • Ma T, Frigeri A, Hasegawa H, Verkman AS (1994) Cloning of a water channel homolog expressed in brain meningeal cells and kidney collecting duct that functions as a stilbene-sensitive glycerol transporter. J Biol Chem 269(34):21845–21849

    CAS  PubMed  Google Scholar 

  • Ma T, Song Y, Yang B et al (2000) Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels. Proc Natl Acad Sci U S A 97(8):4386–4391

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McMahon M, Itoh K, Yamamoto M et al (2001) The Cap’n’Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes. Cancer Res 61(8):3299–3307

    CAS  PubMed  Google Scholar 

  • McWalter GK, Higgins LG, McLellan LI et al (2004) Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. J Nutr 134(12 Suppl):3499S–3506S

    CAS  PubMed  Google Scholar 

  • Pi J, Qu W, Reece JM, Kumagai Y, Waalkes MP (2003) Transcription factor Nrf2 activation by inorganic arsenic in cultured keratinocytes: involvement of hydrogen peroxide. Exp Cell Res 290(2):234–245

    Article  CAS  PubMed  Google Scholar 

  • Stevens JT, Hall LL, Farmer JD, DiPasquale LC, Chernoff N, Durham WF (1977) Disposition of 14C and/or 74As-cacodylic acid in rats after intravenous, intratracheal, or peroral administration. Environ Health Perspect 19:151–157

    PubMed Central  CAS  PubMed  Google Scholar 

  • Vahter M, Marafante E, Lindgren A, Dencker L (1982) Tissue distribution and subcellular binding of arsenic in marmoset monkeys after injection of 74As-arsenite. Arch Toxicol 51:65–72

    Article  CAS  Google Scholar 

  • Waalkes MP, Fox DA, States JC, Patierno SR, McCabe MJ Jr (2000) Metals and disorders of cell accumulation: modulation of apoptosis and cell proliferation. Toxicol Sci 56(2):255–261

    Article  CAS  PubMed  Google Scholar 

  • Wang XJ, Sun Z, Chen W, Eblin KE, Gandolfi JA, Zhang DD (2007) Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonous acid toxicity. Toxicol Appl Pharmacol 225(2):206–213

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Waters SB, Devesa V, Del Razo LM, Styblo M, Thomas DJ (2004) Endogenous reductants support the catalytic function of recombinant rat cyt19, an arsenic methyltransferase. Chem Res Toxicol 17(3):404–409

    Article  CAS  PubMed  Google Scholar 

  • Wysocki R, Chery CC, Wawrzycka D et al (2001) The glycerol channel Fps1p mediates the uptake of arsenite and antimonite in Saccharomyces cerevisiae. Mol Microbiol 40(6):1391–1401

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Seiichiro Himeno.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sumi, D., Tsurumoto, M., Yoshino, Y. et al. High accumulation of arsenic in the esophagus of mice after exposure to arsenite. Arch Toxicol 89, 1751–1758 (2015). https://doi.org/10.1007/s00204-014-1326-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-014-1326-3

Keywords

Navigation