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Cytotoxic and Genotoxic Effects of Titanium Dioxide Nanoparticles in Testicular Cells of Male Wistar Rat

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Abstract

Serious concerns have been expressed about potential risks of engineered nanoparticles. Regulatory health risk assessment of such particles has become mandatory for the safe use in consumer products and medicines; also, the potential effects on reproduction and fertility are relevant for this risk evaluation. In the present study, we examined the effects of intravenously injected titanium dioxide nanoparticles (TiO2-NPs; 21 nm), with special emphasis on reproductive system. Antioxidant enzymes such as catalase, glutathione peroxidase, and superoxide dismutase showed a significant decrease, while significant increase in lipid peroxidase was observed. Our results confirmed the bioaccumulation of TiO2-NPs in testicular cells. In TiO2-NPs-treated animals, various functional and pathological disorders, such as reduced sperm count, increase in caspase-3 (a biomarker of apoptosis), creatine kinase activity, DNA damage, and cell apoptosis were observed. Moreover, the testosterone activity was decreased significantly in a dose-dependent manner in the animals treated with TiO2-NPs as compared with control group animals. It is concluded that TiO2-NPs induce oxidative stress, which produce cytotoxic and genotoxic changes in sperms which may affect the fertilizing potential of spermatozoa.

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References

  1. Mazzola, L. (2003). Commercialising nanotechnology. Nature Biotechnology, 21, 1137–1143.

    Article  CAS  Google Scholar 

  2. Paull, R., Wolfe, J., Hebert, P., & Sinkula, M. (2003). Investing in nanotechnology. Nature Biotechnology, 21, 1144–1147.

    Article  CAS  Google Scholar 

  3. Salata, O. V. (2004). Applications of nanoparticles in biology and medicine. Journal Nanobiotechnology, 2, 3.

    Article  Google Scholar 

  4. Nel, A., Xia, T., Madler, L., & Li, N. (2006). Toxic potential of nanomaterials at the nanolevel. Science, 311, 622–627.

    Article  CAS  Google Scholar 

  5. Donaldson, K., Stone, V., Tran, C. L., Kreyling, W., & Borm, P. J. A. (2004). Nanotoxicology. Occupational and Environmental Medicine, 61, 727–728.

    Article  CAS  Google Scholar 

  6. Hoet, P. H. M., Bruske-Hohlfeld, I., & Salata, O. V. (2004). Nanoparticles known and unknown health risks. Journal Nanobiotechnology, 2, 12.

    Article  Google Scholar 

  7. Oberdorster, G., Oberdorster, E., & Oberdorster, J. (2005). Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives, 113, 823–839.

    Article  CAS  Google Scholar 

  8. Newman, M. D., Stotland, M., & Ellis, J. I. (2009). The safety of nanosized particles in titanium dioxide–and zinc oxide–based sunscreens. Journal of the American Academy of Dermatology, 61(4), 685–692.

    Article  CAS  Google Scholar 

  9. Meena, R., & Paulraj, R. (2012). Oxidative stress mediated cytotoxicity of TiO2 nano anatase in liver and kidney of Wistar rat. Toxicological and Environmental Chemistry, 94(1), 146–163.

    Article  CAS  Google Scholar 

  10. Gurr, J., Wang, A. A. S., Chen, C., & Jan, K. (2005). Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology, 213, 66–73.

    Article  CAS  Google Scholar 

  11. De Jong, W. H., Hagens, W. I., Krystek, P., Burger, M. C., Sips, A. J., & Geertsma, R. E. (2008). Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials, 29, 1912–1919.

    Article  Google Scholar 

  12. Lankveld, D. P., Oomen, A. G., Krystek, P., Neigh, A., Troost-de, J. A., Noorlander, C. W., Van Eijkeren, J. C., Geertsma, R. E., & De Jong, W. H. (2010). The kinetics of the tissue distribution of silver nanoparticles of different sizes. Biomaterials, 31, 8350–8361.

    Article  CAS  Google Scholar 

  13. Yoshida, S., Ono, N., Tsukue, N., Oshio, S., Umeda, T., Takano, H., & Takeda, K. (2006). In utero exposure to diesel exhaust increased accessory reproductive gland weight and serum testosterone concentration in male mice. Environmental Sciences, 13, 139–147.

    CAS  Google Scholar 

  14. Asare, N., Instanesa, C., Sandberga, W. J., Refsnesa, M., Schwarzea, P., Kruszewskib, M., & Brunborg, G. (2012). Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology, 291, 65–72.

    Article  CAS  Google Scholar 

  15. Braydich-Stolle, L., Hussain, S., Schlager, J. J., & Hofmann, M. C. (2005). In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicological Sciences, 88(2), 412–419.

    Article  CAS  Google Scholar 

  16. Ema, M., Kobayashi, N., Naya, M., Hanai, S., & Nakanishi, J. (2010). Reproductive and developmental toxicity studies of manufactured nanomaterials. Reproductive Toxicology, 30, 343–352.

    Article  CAS  Google Scholar 

  17. Chen, Y., Xue, Z., Zheng, D., Xia, K., Zhao, Y., Liu, T., Long, Z., & Zia, J. (2003). Sodium chloride modified silica nanoparticles as a non viral vector with a high efficiency of DNA transfer into cells. Current Gene Therapy, 3, 273–279.

    Article  CAS  Google Scholar 

  18. Kim, J. S., Sung, J. H., Ji, J. H., Song, K. S., Lee, J. H., Kang, C. S., & Yu, I. J. (2011). In vivo genotoxicity of silver nanoparticles after 90-day silver nanoparticle inhalation exposure. Safety Health Work, 2, 34–38.

    Article  CAS  Google Scholar 

  19. Cayli, S., Sakkas, D., Vigue, L., Demir, R., & Huszar, G. (2004). Cellular maturity and apoptosis in human sperm: creatine kinase, caspase-3 and Bcl-XL levels in mature and diminished maturity sperm. Molecular Human Reproduction, 10, 365–372.

    Article  CAS  Google Scholar 

  20. Ceruti, S., Beltrami, E., Matarrese, P., Mazzola, A., Cattabeni, F., & Malorni, W. (2003). A key role for caspase-2 and caspase-3 in the apoptosis induced by 2-chloro-2'-deoxy-adenosine (cladribine) and 2-chloro-adenosine in human astrocytoma cells. Molecular Pharmacology, 63, 1437–1447.

    Article  CAS  Google Scholar 

  21. Riedl, S. J., & Shi, Y. (2004). Molecular mechanisms of caspase regulation during apoptosis. Nature Reviews Molecular Cell Biology, 5, 897–907.

    Article  CAS  Google Scholar 

  22. Pommier, Y., Sordet, O., Antony, S., Hayward, R. L., & Kohn, K. W. (2004). Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene, 23, 2934–2949.

    Article  CAS  Google Scholar 

  23. Hallak, J., Sharma, R. K., Pasqualotto, F. F., Ranganathan, P., Thomas, A. J., & Agarwal, A. (2001). Creatine kinase as an indicator of sperm quality and maturity in men with oligospermia. Urology, 58, 446–451.

    Article  CAS  Google Scholar 

  24. Wallimann, T., Moser, H., Zurbriggen, B., Wegmann, G., & Eppenberger, H. M. (1986). Creatine kinase isoenzymes in spermatozoa. Journal of Muscle Research and Cell Motility, 7, 25–34.

    Article  CAS  Google Scholar 

  25. Kavanagh, J. P., & Darby, C. (1983). Creatine kinase and ATPase in human seminal fluid and prostatic fluid. Journal of Reproduction and Fertility, 68, 51–56.

    Article  CAS  Google Scholar 

  26. Huszar, G., Corrales, M., & Vigue, L. (1988). Correlation between sperm creatine phosphokinase activity and sperm concentrations in normospermic and oligospermic men. Gamete Research, 19, 67–75.

    Article  CAS  Google Scholar 

  27. Huszar, G., Vigue, L., & Corrales, M. (1988). Sperm creatine phosphokinase activity as a measure of sperm quality in normospermic, variablespermic, and oligospermic men. Biology of Reproduction, 38, 1061–1066.

    Article  CAS  Google Scholar 

  28. Huszar, G., & Vigue, L. (1993). Incomplete development of human spermatozoa is associated with increased creatine phosphokinase concentration and abnormal head morphology. Molecular Reproduction and Development, 34, 292–298.

    Article  CAS  Google Scholar 

  29. Marklund, S., & Marklund, G. (1974). Involvement of the superoxide anion radical in autoxidation of pyrogallol as a convenient assay for superoxide dismutase. European Journal of Biochemistry, 47, 469–474.

    Article  CAS  Google Scholar 

  30. Aebi, H. (1974). Catalase. In Bergmeyer (ed.), Methods of Enzymatic. Analysis, 2, 673–684. New York: Academic Press.

  31. Mills, G. C. (1959). The purification and properties of glutathione peroxidase of erythrocytes. Journal of Biological Chemistry, 234, 502.

    CAS  Google Scholar 

  32. Varshney, R., & Kale, R. K. (1990). Effect of calmodulin antagonist on radiation-induced lipid peroxidation in microsomes. International Journal of Radiation Biology, 58, 733–743.

    Article  CAS  Google Scholar 

  33. Kumar, S., Kesari, K. K., & Behari, J. (2011). The therapeutic effect of a pulsed electromagnetic field on the reproductive patterns of male Wistar rats exposed to a 2.45-GHz microwave field. Clinics, 66(7), 1237–1245.

    Article  Google Scholar 

  34. Paulraj, R., & Behari, J. (2006). Single strand DNA breaks in rat brain cells exposed to microwave radiation. Mutation Research, 596, 76–80.

    Article  CAS  Google Scholar 

  35. Gong, J. P., Traganos, F., & Darzynkiewicz, Z. (1994). A selective procedure for DNA extraction from apoptotic cells applicable for gel electrophoresis and flow cytometry. Analytical Biochemistry, 218(2), 314–319.

    Article  CAS  Google Scholar 

  36. Tiwari, D. K., Jin, T., & Behari, J. (2011). Dose-dependent in-vivo toxicity assessment of silver nanoparticle in Wistar rats. Toxicology Mechanisms and Methods, 21(1), 13–24.

    Article  CAS  Google Scholar 

  37. Simeonova, P. P., & Lusster, M. T. (1995). Iron and reactive oxygen species in the asbestos-induced tumour necrosis factor a response from alveolar macrophages. American Journal of Respiratory Cell and Molecular Biology, 12(6), 676–683.

    Article  CAS  Google Scholar 

  38. Zhao, X., Sheng, L., Wang, L., Hong, J., Yu, X., Sang, X., & Hong, F. (2014). Mechanisms of nanosized titanium dioxide-induced testicular oxidative stress and apoptosis in male mice. Particle and Fibre Toxicology, 11(1), 47.

    Article  Google Scholar 

  39. Chaudhari, M., Jayaraj, R., Bhaskar, A. S. B., & Lakshmana, R. (2009). Oxidative stress induction by T-2 toxin causes DNA damage and triggers apoptosis via caspase pathway in human cervical cancer cells. Toxicology, 262, 153–161.

    Article  CAS  Google Scholar 

  40. Da Silva Paula, M. M., da Costa, C. S., Baldin, M. C., Scaini, G., Rezin, G. T., Segala, K., & Streckb, E. L. (2009). In vitro effect of silver nanoparticles on creatine kinase activity. Journal of the Brazilian Chemical Society, 20(8), 1556–1560.

    Article  Google Scholar 

  41. Hemmati, P. G., Normand, G., Gillissen, B., Wendt, J., Dorken, B., & Daniel, P. T. (2008). Cooperative effect of p21Cip1/WAF-1 and 14-3-3sigma on cell cycle arrest and apoptosis induction by p14ARF. Oncogene, 27, 6707–6719.

    Article  CAS  Google Scholar 

  42. Guo, L. L., Liu, X. H., Qin, D. X., Gao, L., Zhang, H. M., Liu, J. Y., & Cui, Y. G. (2009). Effects of nanosized titanium dioxide on the reproductive system of male mice. National Journal of Andrology, 15(6), 517.

    CAS  Google Scholar 

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Meena, R., Kajal, K. & R., P. Cytotoxic and Genotoxic Effects of Titanium Dioxide Nanoparticles in Testicular Cells of Male Wistar Rat. Appl Biochem Biotechnol 175, 825–840 (2015). https://doi.org/10.1007/s12010-014-1299-y

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