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Effects of Chronic Cadmium Poisoning on Zn, Cu, Fe, Ca, and Metallothionein in Liver and Kidney of Rats

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Abstract

An experiment was conducted to invest effects of chronic cadmium poisoning on Zn, Cu, Fe, Ca, and metallothionein gene expression and protein synthesis in liver and kidney in rats. Forty rats, 6 weeks old, were randomly allocated into two groups. A group was given CdCl2 (1 mg/KgCd2+) by intraperitoneal injection once a day. The other group was treated with normal saline in the same way. Liver and kidney were collected for analysis at the end of the third week. Results showed that Cd exposure increased Cd (P < 0.01) and Zn (P < 0.01) content both in liver and kidney. Fe and Ca concentration had a considerable increase in kidney (P < 0.01), while both had different degree reduction in liver. Discrepancies between MT mRNA and protein were observed in liver and kidney. In liver, both MT mRNA and protein had a significant increase (P < 0.01), while in kidney, only MT gene increase was checked. Meanwhile, the expression levels of MT-1 mRNA and MT-2 mRNA were distinct between liver and kidney. The present study indicated that changes in tissue Cd and Zn levels tended to reflect MT mRNA expression, but bear no clear relationship with MT protein. There did not have a strict dose-dependent relationship among Cd content, MT gene expression, and MT protein synthesis. What is more, changes of Zn, Fe, Cu, and Ca had a certain interaction with both MT mRNA and protein.

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Abbreviations

MT:

Metallothionein

ICP-MS:

Inductively coupled plasma mass spectrometry

MTF-1/2:

Metalloregulatory transcription factor 1/2

MRE:

Metal response element

PKC:

Protein kinase C

ROS:

Reactive oxygen species

PMSF:

Phenylmethanesulfonyl fluoride

References

  1. Risso-de Faverney C, Orsini N, de Sousa G et al (2004) Cadmium-induced apoptosis through the mitochondrial pathway in rainbow trout hepatocytes: involvement of oxidative stress. Aquat Toxicol 69:247–258

    Article  PubMed  CAS  Google Scholar 

  2. Danijela D-C, Curcic JM, Bulat ZP (2008) Relation between lipid peroxidation and iron concentration in mouse liver after acute and subacute cadmium intoxication. J Trace Elem Med Biol 22:66–72

    Article  Google Scholar 

  3. Shen H-M, Dong S-Y, Ong C-N (2001) Critical role of calcium overloading in cadmium-induced apoptosis in mouse thymocytes. Toxicol Appl Pharmacol 171:12–19

    Article  PubMed  CAS  Google Scholar 

  4. Wang Y, Fang J, Leonard SS, Rao KMK (2004) Cadmium inhibits the electron transfer chain and induces reactive oxygen species. Free Radic Biol Med 36:1434–1443

    Article  PubMed  CAS  Google Scholar 

  5. Don KS, Kyu MC, Su-Yong E et al (2008) Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis. Biochem Biophys Res Commun 1(328):326–334

    Google Scholar 

  6. Gunn SA, Gould TC, Anderson WAD (1963) Cadmium-induced interstitial cells tumors in rats and mice and their prevention by zinc. J Natl Cancer Inst 31:745–759

    PubMed  CAS  Google Scholar 

  7. Shiraishi N, Nochades JF, Coogan TP (1995) Sensitivity to cadmium-induced genotoxicity in rat testicular cells is associated with minimal expression of the metallothionein gene. Toxicol Appl Pharmacol 130:229–236

    Article  PubMed  CAS  Google Scholar 

  8. Nordberg M, Nordberg GF (2000) Toxicological aspects of metallothionein. Cell Mol Biol 46:451–463

    PubMed  CAS  Google Scholar 

  9. Klaassen CD, Liu J, Choudhur S (1999) Metallothionein: an intracellular protein to protect against cadmium toxicity. Annu Rev Pharmacol Toxicol 39:267–294

    Article  PubMed  CAS  Google Scholar 

  10. Patrice G, Magalie B, Alain B (2006) Comparative effects of direct cadmium contamination on gene expression in gills, liver, skeletal muscles and brain of the zebrafish. BioMetals 19:225–235

    Article  Google Scholar 

  11. Vasconcelos MH, Tam S-C, Hesketh JE, Reid M, Beattie JH (2002) Metal-and tissue-dependent relationship between metallothionein mRNA and protein. Toxicol Appl Pharmacol 182:91–97

    Article  PubMed  CAS  Google Scholar 

  12. Lucia M, Andre J-M (2010) Effects of dietary cadmium contamination on bird Anas platyrhynchos—Comparison with species Cairina moschata. Ecotoxicol Environ Saf 738:2010–2016

    Article  Google Scholar 

  13. Formigare A, Irato P et al (2007) Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects. Comparative Biochemistry and Physiology C-Toxicology & Pharmacology 146(4):443–459

    Article  Google Scholar 

  14. Cherian MG, Apostolova MD (2000) Nuclear localization of metallothionein during cell proliferation and differentiation. Cell Mol Biol 46:347–356

    PubMed  CAS  Google Scholar 

  15. Klassen RB, Crenshaw K, Kozyraki R, Verroust PJ, Tio L, Atrian S, Allen PL, Hammond TG (2004) Megalin mediates renal uptake of heavy metal metallothionein complexes. Am J Physiol Renal Physiol 287:393–403

    Article  Google Scholar 

  16. Vig PJ, Bhatia M, Gill KD, Nath R (1989) Cadmium inhibits brain calmodulin: in vitro and in vivo studies. Bull Environ Contam Toxicol 43:541–547

    Article  PubMed  CAS  Google Scholar 

  17. Verbost PM, Flik G, Lock RA, Wendelaar Bonga SE (1987) Cadmium inhibition of Ca2+ uptake in rainbow trout gills. Am J Physiol 253:216–221

    Google Scholar 

  18. Takahashi Y, Ogra Y, Suzuki KT (2005) Nuclear trafficking of metallothionein requires oxidation of a cytosolic partner. J Cell Physiol 202:563–569

    Article  PubMed  CAS  Google Scholar 

  19. Benters J, Flogel U, Schafer T, Leibfritz D, Hechtenberg S, Beyersmann D (1997) Study of the interactions of cadmium and zinc ions with cellular calcium homoeostasis using 19F-NMR spectroscopy. Biochem J 322(3):793–799

    PubMed  CAS  Google Scholar 

  20. Formigari A, Santon A, Irato P (2007) Efficacy of zinc treatment against iron-induced toxicity in rat hepatoma cell line H4-II-E-C3. Liver Int 27:120–127

    Article  PubMed  CAS  Google Scholar 

  21. Feng W, Cai J, Pierce WM, Franklin RB, Maret W, Benz FW, Kang YJ (2005) Metallothionein transfers Zn to mitochondrial aconitase through a direct interaction in mouse hearts. Biochem Biophys Res Commun 332:853–858

    Article  PubMed  CAS  Google Scholar 

  22. Garrett SH, Xiong X, Arizono K, Brady FO (1992) Phorbol ester induction of rat hepatic metallothionein in vivo and in vitro. Int J Biochem 24:1669–1676

    Article  PubMed  CAS  Google Scholar 

  23. Arizono K, Peterson KL, Brady FO (1993) Inhibitors of Ca2+ channels, calmodulin and protein kinases prevent A23187 and other inductions of metallothionein mRNA in EC3 rat hepatoma cells. Life Sci 53:1031–1037

    Article  PubMed  CAS  Google Scholar 

  24. Danijela D-C, Curcic JM, Plamenac BZ (2007) Relation between lipid peroxidation and iron concentration in mouse liver after acute and subacute cadmium intoxication. J Trace Elem Med Biol 221:66–72

    Google Scholar 

  25. Eybl V, Kotyzová D, Leš Etický L, Bludovská M, Koutenský J (2006) The influence of curcumin and manganese complex of curcumin on cadmium-induced oxidative damage and trace elements status in tissues of mice. J Appl Toxicol 26:207–212

    Article  PubMed  CAS  Google Scholar 

  26. Jurczuk M, Brzó Ska MM, Rogalska J, Moniuszko-Jakoniuk J (2003) Iron body status of rats chronically exposed to cadmium and ethanol. Alcohol Alcohol 38(3):202–207

    PubMed  CAS  Google Scholar 

  27. Steinebach OM, Wolterbeek BT (1992) Metallothionein biodegradation in rat hepatoma cells: a compartmental analysis aided 35S-radiotracer study. Biochim Biophys Acta 1116:155–165

    Article  PubMed  CAS  Google Scholar 

  28. Dorian C, Gattone VH II, Klaasen CD (1992) Accumulation and degradation of the protein moiety of cadmium-metallothionein (CdMT) in the mouse kidney. Toxicol Appl Pharmacol 117:242–248

    Article  PubMed  CAS  Google Scholar 

  29. Dudley RE, Gammal LM, Klaasen CD (1985) Cadmium-induced, hepatic and renal injury in chronically exposed rats: likely role of hepatic cadmium-metallothionein in nephrotoxicity. Toxicol Appl Pharmacol 77:414–426

    Article  PubMed  CAS  Google Scholar 

  30. Sendelbach LE, Klaasen CD (1988) Kidney synthesizes less metallothionein than liver in response to cadmium chloride and cadmium-metallothionein. Toxicol Appl Pharmacol 92:95–102

    Article  PubMed  CAS  Google Scholar 

  31. Sabolic I, Ljubojevic M, Herak-Kramberger CM, Brown D (2002) Cd-MT causes endocytosis of brush-border transporters in rat renal proximal tubules. Am J Physiol Renal Physiol 283:1389–1402

    Google Scholar 

  32. Sabolic I, Herak-Kramberger CM, Brown D (2001) Subchronic cadmium treatment affects the abundance and arrangement of cytoskeletal proteins in rat renal proximal tubule cells. Toxicology 165:205–216

    Article  PubMed  CAS  Google Scholar 

  33. Herak-Kramberger CM, Spindler B, Biber J, Murer H, Sabolic I (1996) Renal type II Na/Pi-cotransporter is strongly impaired whereas the Na/sulphate-cotransporter and aquaporin1 are unchanged in cadmium-treated rats. Pflugers Arch 432:336–344

    Article  PubMed  CAS  Google Scholar 

  34. Ghoshal K, Jacob ST (2001) Regulation of metallothionein gene expression. Prog Nucleic Acid Res Mol Biol 66:357–384

    Article  PubMed  CAS  Google Scholar 

  35. Haq F, Mahoney M, Koropatnick A (2003) Signaling events for metallothionein induction. Mutat Res 533:211–226

    Article  PubMed  CAS  Google Scholar 

  36. Wang Y, Fang J, Leonard SS, Krishna Rao KM (2004) Cadmium inhibits the electron transfer chain and induces reactive oxygen species. Free Radic Biol Med 36:1434–1443

    Article  PubMed  CAS  Google Scholar 

  37. Hassoun EA, Stohs SJ (1996) Cadmium-induced production of superoxide anion and nitric oxide, DNA single strand breaks and lactate dehydrogenase leakage in J774A.1 cell cultures. Toxicology 112:219–226

    Article  PubMed  CAS  Google Scholar 

  38. Dian G, Tang WG, Tao CX (2009) Metallothionein-2 gene from the mandarin fish Siniperca chuatsi: cDNA cloning, tissue expression, and immunohistochemical localization. Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 149(1):18–25

    Article  Google Scholar 

  39. Kang YJ (2006) Metallothionein redox cycle and function. Exp Biol Med 231:1459–1467

    CAS  Google Scholar 

  40. Gonzalez P, Baudrimont M (2006) Comparative effects of direct cadmium contamination on gene expression in gills, liver, skeletal muscles and brain of the zebrafish (Danio rerio). BioMetals 193:225–235

    Article  Google Scholar 

  41. Carvan MJ III, Solis WA, Gedamu L, Nebert DW (2000) Activation of transcription factors in zebrafish cell cultures by environmental pollutants. Arch Biochem Biophys 376:320–327

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Fundamental Research Funds for the Central Universities and Huazhong Agricultural University Scientific & Technological Self-innovation Foundation. We thank the members of the veterinary internal medicine laboratory in the College of Veterinary Medicine, Huazhong Agricultural University.

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Correspondence to Jiakui Li.

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Ding Zhang and Jianfeng Gao had the same contribution to this study.

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Zhang, D., Gao, J., Zhang, K. et al. Effects of Chronic Cadmium Poisoning on Zn, Cu, Fe, Ca, and Metallothionein in Liver and Kidney of Rats. Biol Trace Elem Res 149, 57–63 (2012). https://doi.org/10.1007/s12011-012-9394-9

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  • DOI: https://doi.org/10.1007/s12011-012-9394-9

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