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Subcellular changes of essential metal shown by in-air micro-PIXE in oral cadmium-exposed mice

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Abstract

To clarify the relation of essential metals to cadmium (Cd) toxicity, we evaluated metallothionein expression and analyzed the subcellular distribution of essential metals using in-air micro-Particle-Induced X-ray Emission (PIXE). Four mice were dosed orally with 100 mg/L of Cd in drinking water for 1.5 or 2 years. Frozen samples of organs were used for micro-PIXE analysis and formalin-fixed samples were used for metallothionein staining. Immunohistochemically, metallothionein induction by 1.5y-Cd exposure was higher in the renal cortex than in the liver. Metallothionein expression was reduced after 2y-Cd administration compared to the 1.5y-Cd-exposed mice. Cd-induced tissue damage became marked in the 2y-Cd-exposed mice compared to the 1.5y-Cd-exposed mice, in which nephrotoxicity was more prominent than hepatotoxicity. Cd yield was higher in the renal cortex of the 2y-Cd-exposed mouse than in that of the 1.5y-Cd-exposed mouse, whereas no such increasing tendency was found in the liver. Compared to the control, the Cd-exposed mice markedly accumulated zinc in the liver and renal cortex. In the Cd-exposed mice, iron was mildly accumulated in the renal cortex and was slightly deprived in the liver. Elemental maps showed that a large amount of Cd was spatially combined with zinc in the 1.5y-Cd mouse. Free Cd became abundant in the 2y-Cd-exposed mouse. In addition, a small amount of Cd was colocalized with iron. The data suggest that zinc may contribute to protect against oral-administrated Cd toxicity, and impaired induction of MT may participate in hepato-nephrotoxicity of the 2y-Cd-exposed mouse.

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References

  • Andersen O, Nielsen JP, Svendsen P (1988) Oral cadmium chloride intoxication in mice: effects of dose on tissue damage, intestinal absorption and relative organ distribution. Toxicology 48:225–236

    Article  PubMed  CAS  Google Scholar 

  • Bara M, Moretto P, Razafindrabe L, Llabador Y, Simonoff M, Guiet-Bara A (1996) Nuclear microanalysis of the effect of magnesium and taurine on the ionic distribution in the human amniotic membrane. Cell Mol Biol 42:27–38

    PubMed  CAS  Google Scholar 

  • Brzoska MM, Kaminski M, Supernak-Bobko D, Zwierz K, Moniuszko-Jakoniuk (2003) Changes in the structure and function of the kidney of rats chronically exposed to cadmium. I. Biochemical and histopathological studies. Arch Toxicol 77:344–352

    PubMed  CAS  Google Scholar 

  • Cai L, Li XK, Song Y, Cherian MG (2005) Essentiality, toxicology and chelation therapy of zinc and copper. Curr Med Chem 12:2753–2763

    Article  PubMed  CAS  Google Scholar 

  • Casalino E, Sblano C, Landriscina C (1997) Enzyme activity alternation by cadmium administration to rats: The possibility of iron involvement in lipid peroxidation. Arch Biochem Biophys 346:171–179

    Article  PubMed  CAS  Google Scholar 

  • Cherian MG, Cahn HM (1993) Biological function of metallothionein – A review. In: Suzuki KT, Imura N, Kimura M (eds) Metallothionein III. Birkhauser Verlag, Basel, pp 87–109

    Google Scholar 

  • David SR, Cousins RJ (2000) Metallothionein expression in animals: A physiological persective of function. J Nut 130:1085–1088

    Google Scholar 

  • Ercal N, Gurer-Orhan H, Aykin-Bums N (2001) Toxic metals and oxidative stress part1: Mechanism involved in metal induced oxidative damage. Curr Top Med Chem 1:529–539

    Article  PubMed  CAS  Google Scholar 

  • Hansen JM, Zhang H, Jones DP (2006) Differential oxidation of thioredoxin-1, thioredoxin-2, and glutathione by metals ions. Free Radic Biol Med 40:138–145

    Article  PubMed  CAS  Google Scholar 

  • Jarup L, Berglund M, Elinder CG et al (1998) Health effects of cadmium exposure- a review of the literature and a risk estimate. Scand J Work Environ Health 24:1–51

    PubMed  Google Scholar 

  • Jurczuk M, Brzoska MM, Moniuszko-Jakoniuk J, galazyn-Sidorczuk M, Kulikowska-Karpinska E (2004) Antioxidant enzymes activity and lipid peroxidation in liver and kidney of rats exposed to cadmium and ethanol. Food Chem Toxicol 42:429–438

    Article  PubMed  CAS  Google Scholar 

  • Kagi JH, Kojima Y (1987) Chemistry and biochemistry of metallothionein. Experientia Suppl 52:25–61

    PubMed  CAS  Google Scholar 

  • Klassen CD, Liu J, Choudhuri S (1999) Metallothionein: an intracellular protein to protect against cadmium toxicity. Ann Rev Pharmacol Toxicol 39:267–294

    Article  Google Scholar 

  • Liu J, Klassen CD (1996) Absorption and distribution of cadmium in metallothionein-1 transgenic mice. Fundam Appl Toxicol 29:294–300

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Liu L, Habeebu SM, Waalkes MP, Klassen CD (2000) Metallothioenin-I/II null mice are sensitive to chronic oral cadmium-induced nephrotoxicity. Toxicol Sci 57:167–176

    Article  PubMed  CAS  Google Scholar 

  • Martelli A, Moulis JM (2004) Zinc and cadmium specifically interfere with RNA-binding activity of human iron regulatory protein 1. J Inorg Biochem 98:1413–1420

    Article  PubMed  CAS  Google Scholar 

  • Martelli A, Rousselet E, Dycke C, Moulis JM (2006) Cadmium toxicity in animal cells by interference with essential metals. Biochimie 88:1807–1814

    Article  PubMed  CAS  Google Scholar 

  • Mitsumori K, Shibutani M, Sato S et al (1998) Relationship between the development of hepato-renal toxicity and cadmium accumulation in rats given minimum to large amounts of cadmium chloride in the long-term: preliminary study. Arch Toxicol 72:545–552

    Article  PubMed  CAS  Google Scholar 

  • Nagamine T, Kusakabe T, Takada H et al (2006) Interferon beta-induced changes in metallothionein expression and subcellular distribution of zinc in HepG2 cells. Cytokine 34:312–319

    Article  PubMed  CAS  Google Scholar 

  • Noel L, Guerin T, Kolf-Clauw M (2004) Subchronic dietary exposure of rats to cadmium alters the metabolism of metals essential to bone health. Food Chem Toxicol 42:1203–1210

    Article  PubMed  CAS  Google Scholar 

  • Nordberg GF, ** T, Nordberg M (1994) Subcellular target of cadmium bnephrotoxicity: cadmium binding to renal membrane proteins in animals with or without protective metallothionein synthesis. Environ Health Perspect 102:191–194

    Article  PubMed  CAS  Google Scholar 

  • Oishi S, Nakagawa J, Ando M (2000) Effects of cadmium administration on the endogenous metal balance in arts. Biol Tra Ele Res 76:257–278

    CAS  Google Scholar 

  • Partrick L (2003) Toxic metals and antioxidants: Part II. The role of antioxidant in arsenic and cadmium toxicity. Altern Med Rev 8:106–128

    Google Scholar 

  • Pourahmad J, O’Brien P, Jokar F, Daraei B (2003) Carcinogenesis metal induced sites of reactive oxygen species formation in hepatocyte. Toxicol in Vitro 17:803–810

    Article  PubMed  CAS  Google Scholar 

  • Sakai T, Kamiya T, Oikawa M, Sato T, Tanaka A, Ishii K (2002) JAERI Takasaki in-air micro-PIXE system for various applications. Nucl Instr Meth B190:271–275

    Google Scholar 

  • Sakai T, Oikawa M, Sato T, Nagamine T, Moon HD, Nakazato K, Suzuki K (2005) New in-air micro-PIXE system for biological applications. Nucl Instr Meth B231:112–116

    Google Scholar 

  • Satarug S, Baker Jr, Reilly PEB, Moore MR, Williams DJ (2001) Changes in zinc and copper homeostasis in human livers and kidneys associated with exposure to environmental cadmium. Hum Exp Toxicol 20:205–213

    Article  PubMed  CAS  Google Scholar 

  • Shibutani M, Mitsumori K, Satoh S et al (2001) Relationship betweeen toxicity and cadmium accumulation in rats given low amounts of cadmium chloride or cadmium-polluted rice for 22 months. J Toxicol Sci 26:337–358

    Article  PubMed  CAS  Google Scholar 

  • Shimoda R, Achanzar WE, Qu W, Nagamine T, Takagi H, Mori M, Waalkes MP (2003) Metallothionein is a potential negative regular of apoptosis. Toxcol Sci 73:294–300

    Article  CAS  Google Scholar 

  • Swiergosz-Kowalewska, Holewa I (2006) Cadmium, zinc and iron interactions in the tissues of bank vole Clethrionomys glareolus after exposure to low and high doses of cadmium chloride. BioMetals (in press)

  • Valko M, Morris H, Cronin MTD (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–208

    Article  PubMed  CAS  Google Scholar 

  • Waalkes MP (2003) Cadmium carcinogenesis. Mutat Res 533:107–120

    PubMed  CAS  Google Scholar 

  • Watjen W, Beyersmann D (2004) Cadmium-induced apoptosis in C6 glioma cells: Influence of oxidative stress. BioMetals 17:65–78

    Article  PubMed  Google Scholar 

  • WHO. (1993) Cadmium. In evaluation of certain food additives and contaminations. Forty-first report of the joint FAO/WHO Expert Committee on Food Additives. WHO technical report series, WHO, Geneva

  • Wlostowski T, Krasowska A, Laszkiewicz-Tiszczenko B (2000) Dietary cadmium induces histopathological changes despite a sufficient metallothionein level in the liver and kidney of the bank vole (Clethrionomys glareolus). Comp Biochem Physiol C 126:21–28

    CAS  Google Scholar 

Download references

Acknowledgment

This work was supported in part by the 21st Century COE Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. School of Health Sciences, Faculty of Medicine, Gunma University, 3-39-15 Shouwa-machi, Maebashi, Gunma, 371-8514, Japan

    Kyoumi Nakazato, Takeaki Nagamine, Keij Suzuki, Takahiko Kusakabe & H. D. Moon

  2. 21st Century COE Program, Graduate School of Medicine, Gunma University, 3-39-22 Shouwa-machi, Maebashi, Gunma, 371-8511, Japan

    Takeaki Nagamine, Takahiko Kusakabe, Masakazu Oikawa, Takuro Sakai & Kazuo Arakawa

  3. Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute, 233 Watanuki-machi, Takasaki, Gunma, 370-1292, Japan

    Masakazu Oikawa & Kazuo Arakawa

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  1. Kyoumi Nakazato
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  2. Takeaki Nagamine
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  3. Keij Suzuki
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  4. Takahiko Kusakabe
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Correspondence to Kyoumi Nakazato.

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Nakazato, K., Nagamine, T., Suzuki, K. et al. Subcellular changes of essential metal shown by in-air micro-PIXE in oral cadmium-exposed mice. Biometals 21, 83–91 (2008). https://doi.org/10.1007/s10534-007-9095-6

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  • DOI: https://doi.org/10.1007/s10534-007-9095-6

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