Acta Biologica Hungarica

, Volume 60, Issue 1, pp 55–67 | Cite as

Preliminary Studies on the Effect of Zinc and Selenium on Vanadium-Induced Cytotoxicity in vitro

  • Iwona ZwolakEmail author
  • Halina Zaporowska


In the present work, we investigated the cytotoxicity of vanadium and the influence of zinc and selenium on vanadium-dependent cell damage in the BALB/c 3T3 cell culture. Treatment of cells for 24 hours with medium containing 50, 100 and 200 μM NaVO3 caused a. significant decrease in the cell viability as measured by MTT test. Furthermore, the assays for reactive oxygen species (NBT reduction and phenol red oxidation) demonstrated the increase in superoxide and hydrogen peroxide production. In the cotreatment studies, the cells were exposed to NaVO3 (50, 100 and 200 μM) in the presence of nontoxic concentrations of ZnCl2 (5 μM) or Na2SeO3 (0.5 μM). Following 24 h. incubation, the cell viability (assessed in MTT assay) and reactive oxygen species generation were evaluated. Our data suggest that zinc and selenium, in the concentrations mentioned above, provide no protection against adverse actions induced by sodium metavanadate at concentration levels of 50, 100 and 200 μM. To our knowledge, this is the first report from in vitro studies on interaction between pentavalent vanadium and trace elements that function as antioxidants: zinc and selenium.


Cell culture vanadium zinc selenium reactive oxygen species 


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  1. 1.
    Bay, B. H., Sit, K. H., Paramanantham, R., Chan, Y. G. (1997) Hydroxyl free radicals generated by vanadyl[IV] induce cell blebbing in mitotic human Chang liver cells. BioMetals 10, 119–122.CrossRefGoogle Scholar
  2. 2.
    Capella, L. S., Gefe, M. R., Silva, E. F., Affonso-Mitidieri, O., Lopes, A. G., Rumjanek, V. M., Capella, M. A. M. (2002) Mechanisms of vanadate-induced cellular toxicity: role of cellular glutathione and NADPH. Arch. Biochem. Biophys. 406, 65–72.CrossRefGoogle Scholar
  3. 3.
    Chakraborty, T., Chatterjee, A., Saralaya, M. G., Dhachinamoorthi, D., Chatterjee, M. (2006) Vanadium inhibits the development of 2-acetylaminofluorene-induced premalignant phenotype in a. two-stage chemical rat hepatocarcinogenesis model. Life Sci. 78, 2839–2851.CrossRefGoogle Scholar
  4. 4.
    Chen, C., Yu, H., Zhao, J., Li, B., Qu, L., Liu, S., Zhang, P., Chai, Z. (2006) The roles of serum selenium and selenoproteins on mercury toxicity in environmental and occupational exposure. Environ. Health Perspect. 114, 297–301.CrossRefGoogle Scholar
  5. 5.
    Cortizo, A. M., Bruzzone, L., Molinuevo, S., Etcheverry, S. B. (2000) A. possible role of oxidative stress in the vanadium-induced cytotoxicity in the MC3T3E1 osteoblast and UMR106 osteosarcoma cell lines. Toxicology 147, 89–99.CrossRefGoogle Scholar
  6. 6.
    Cortizo, A. M., Salice, V. C., Vescina, C. M., Etcheverry, S. B. (1997) Proliferative and morphological changes induced by vanadium compounds on Swiss 3T3 fibroblasts. BioMetals 10, 127–133.CrossRefGoogle Scholar
  7. 7.
    Demelash, A., Karlsson, J. O., Nilsson, M., Bjorkman, U. (2004) Selenium has a. protective role in caspase-3-dependent apoptosis induced by H2O2 in primary cultured pig thyrocytes. Eur J. Endocrinol. 150, 841–849.CrossRefGoogle Scholar
  8. 8.
    Evangelou, A. M. (2002) Vanadium in cancer treatment. Crit. Rev. Oncol. Hematol. 42, 249–265.CrossRefGoogle Scholar
  9. 9.
    Fischer, A. B., Skreb, Y. (2001) In vitro toxicology of heavy metals using mammalian cells: an overview of collaborative research data. Arh. Hig. Rada Toksikol. 52, 333–354.PubMedGoogle Scholar
  10. 10.
    Gaetke, L. M., Chow, C. K. (2003) Copper toxicity, oxidative stress and antioxidant nutrients. Toxicology 189, 147–163.CrossRefGoogle Scholar
  11. 11.
    Garcia, J. J., Martinez-Ballarin, E., Millan-Plano, S., Allue, J. L., Albendea, C., Fuentes, L., Escanero, J. F. (2005) Effects of trace elements on membrane fluidity. J. Trace Elem. Med. Biol. 19, 19–22.CrossRefGoogle Scholar
  12. 12.
    Gurer, H., Ercal, N. (2000) Can antioxidants be beneficial in the treatment of lead poisoning. Free Radical Biol. Med. 29, 927–945.CrossRefGoogle Scholar
  13. 13.
    Haider, S. S., Abdel-Gayoum, A. A., El-Fakhri, M., Ghwarsha, K. M. (1998) Effect of selenium on vanadium toxicity in different regions of rat brain. Hum. Exp. Toxicol. 17, 23–28.CrossRefGoogle Scholar
  14. 14.
    Hsu, P. C., Guo, Y. L. (2002) Antioxidant nutrients and lead toxicity. Toxicology 180, 33–44.CrossRefGoogle Scholar
  15. 15.
    Huang, C., Zhang, Z., Ding, M., Li, I., Ye, I., Leonard, S. S., Shen, H. M., Butterworth, L., Lu, Y., Costa, M., Rojanasakul, Y., Castranova, V., Vallyathan, V., Shi, X. (2000) Vanadate induces p53 transactivation through hydrogen peroxide and causes apoptosis. J. Biol. Chem. 275, 32516–32522.CrossRefGoogle Scholar
  16. 16.
    Mazzotti, E., Sabbioni, E., Ghiani, M., Cocco, B., Ceccatelli, R., Fortaner, S. (2001) In vitro assessment of cytotoxicity and carcinogenic potential of chemicals: evaluation of the cytotoxicity induced by 58 metal compounds in the Balb/3T3 cell line. ATLA 29, 601–611.PubMedGoogle Scholar
  17. 17.
    Mazzotti, F., Sabbioni, E., Ponti, J., Ghiani, M., Fortaner, S., Rossi, G. L. (2002) In vitro setting of dose-effect relationship of 32 metal compounds in the Balb/3T3 cell line, as a. basis for predicting their carcinogenic potential. ATLA 30, 209–217.PubMedGoogle Scholar
  18. 18.
    Morinville, A., Maysinger, D., Shaver, A. (1998) From Vanadis to Atropos: vanadium compounds as pharmacological tools in cell death signalling. TIPS 19, 452–460.PubMedGoogle Scholar
  19. 19.
    Mukherjee, B., Patra, B., Mahapatra, S., Benerjee, P., Tiwari, A., Chatterjee, M. (2004) Vanadium-an element of atypical biological significance. Toxicol. Lett. 150, 135–143.CrossRefGoogle Scholar
  20. 20.
    Pick, E. (1986) Microassays for superoxide and hydrogen peroxide production and nitroblue tetra-zolium reduction using an enzyme immunoassay microplate reader. Methods Enzymol. 132, 407–421.CrossRefGoogle Scholar
  21. 21.
    Powell, S. R. (2000) The antioxidant properties of zinc. J. Nutr. 130, 1447S-1454S.Google Scholar
  22. 22.
    Putnam, K. P., Bombick, D. W., Doolittle, D. J. (2002) Evaluation of eight in vitro assays for assessing the cytotoxicity of cigarette smoke condensate. Toxicol. In Vitro 16, 599–607.CrossRefGoogle Scholar
  23. 23.
    Rao, A. V. S., Ravishankar, H. N., Ramasarma, T. (1998) Diperoxovanadate participates in peroxidation reactions of H2O2 in presence of abundant catalase. Biochim. Biophys. Acta 1381, 249–255.CrossRefGoogle Scholar
  24. 24.
    Riley, M. R., Boesewetter, D. E., Kim, A. M., Sirvent, F. P. (2003) Effects of metals Cu, Fe, Ni, V., and Zn on rat lung epithelial cells. Toxicology 190, 171–184.CrossRefGoogle Scholar
  25. 25.
    Rossman, T. G., Uddin, A. N. (2004) Selenium prevents spontaneous and arsenite-induced mutagenesis. Int. Congr. Ser. 1275, 173–179.CrossRefGoogle Scholar
  26. 26.
    Rudolf, E., Cervinka, M., Cerman, J. (2005) Zinc has ambiguous effects on chromium (Vl)-induced oxidative stress and apoptosis. J. Trace Elem. Med. Biol. 18, 251–260.CrossRefGoogle Scholar
  27. 27.
    Shechter, Y., Goldwaser, I., Mironchik, M., Fridkin, M., Gefel, D. (2003) Historic perspective and recent developments on the insulin-like actions of vanadium; toward developing vanadium-based drugs for diabetes. Coord. Chem. Rev. 237, 3–11.CrossRefGoogle Scholar
  28. 28.
    Shimizu, M., Hochadel, J. F., Fulmer, B. A., Waalkes, M. P. (1998) Effect of glutathione depletion and metallothionein gene expression on arsenic-induced cytotoxicity and c-myc expression in vitro. Toxicol. Sci. 45, 204–211.PubMedGoogle Scholar
  29. 29.
    Stefanidou, M., Maravelias, C., Dona, A., Spiliopoulou, C. (2006) Zinc: a. multipurpose trace element. Arch. Toxicol. 80, 1–9.CrossRefGoogle Scholar
  30. 30.
    Szuster-Ciesielska, A., Stachura, A., Slotwinska, M., Kaminska, T., Sniezko, R., Paduch, R., Abramczyk, D., Filar, J., Kandefer-Szerszen, M. (2000) The inhibitory effect of zinc on cadmium-induced cell apoptosis and reactive oxygen species (ROS) production in cell cultures. Toxicology 145, 159–171.CrossRefGoogle Scholar
  31. 31.
    Valko, M., Morris, H., Cronin, M. T. (2005) Metals, toxicity and oxidative stress. Curr Med. Chem. 12, 1161–1208.CrossRefGoogle Scholar
  32. 32.
    Vanadium. In: Air Quality Guidelines - Second Edition. WHO Regional Office for Europe, Copenhagen, Denmark, 2000, Chapter 6.12, pp. 1–9.Google Scholar
  33. 33.
    Watjen, W., Cox, M., Biagioli, M., Beyersmann, D. (2002) Cadmium-induced apoptosis in C6 glioma cells: mediation by caspase-9 activation. BioMetals 15, 15–25.CrossRefGoogle Scholar
  34. 34.
    Zaporowska, H., Scibior, A. (1999) Activity of neutrophilic granulocytes in rats following intoxication with vanadium and zinc. Folia Histochem. Cytobiol. 37, 113–114.PubMedGoogle Scholar
  35. 35.
    Zaporowska, H., Wasilewski, W. (1992) Haematological effects of vanadium on living organisms. Comp. Biochem. Physiol. 102C, 223–231.Google Scholar
  36. 36.
    Zaporowska, H., Wasilewski, W. (1992) Combined effect of vanadium and zinc on certain selected haematological indices in rats. Comp. Biochem. Physiol. 103C, 143–147.Google Scholar
  37. 37.
    Zeng, H., Combs, G. F. (2008) Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion. J. Nutr. Biochem. 19, 1–7.CrossRefGoogle Scholar
  38. 38.
    Zhang, Z., Huang, C., Li, I., Leonard, S. S., Lanciotti, R., Butterworth, L., Shi, X. (2001) Vanadate-induced cell growth regulation and the role of reactive oxygen species. Arch. Biochem. Biophys. 392, 311–320.CrossRefGoogle Scholar
  39. 39.
    Zhang, Z., Leonard, S. S., Huang, C., Vallyathan, V., Castranova, V., Shi, X. (2003) Role of reactive oxygen species and MAPKs in vanadate-induced G2/M phase arrest. Free Radic. Biol. Med. 34, 1333–1342.CrossRefGoogle Scholar

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© Akadémiai Kiadó, Budapest 2009

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Department of Cell Biology, Institute of Environmental ProtectionJohn Paul II Catholic University of LublinLublinPoland

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