Characteristics of the response of the microalga (Dunaliella viridis) to cerium compounds in culture

Keywords: bioindicator; cytotoxicity; cerium salts; cerium dioxide nanoparticles


Recently, nanobiotechnology has been developing intensively; therefore, various properties of nanoparticles, which depend on their origin, concentration, and size, are of interest. It is known that CeO2 nanoparticles cause a positive biological effect. These particles are able to penetrate through biomembranes. At the same time, there are assumptions about a high degree of biological risks when using nanomaterials, and it is obvious that the biosafety of nanomaterials is decisive in the development of new products, including for medicine. The cytotoxicity of samples of cerium salts and cerium dioxide nanoparticles of different sizes was assessed at different concentrations using D. viridis. The cytotoxicity level by morphological and functional disorders of D. viridis was investigated, as determined by the change in cell shape, accumulation of inclusions, loss of flagellum, change in nature and movement, the formation of micro- and macroaggregates by D. viridis cells and exometabolite release. The cytotoxicity coefficient was calculated as a quotient of total detected changes divided by their number. It was shown that cerium salts (cerium (IV) ammonium nitrate and cerium (III) chloride) had pronounced cytotoxicity, which exceeded cytotoxicity values of the control by 7 and 6 times, respectively. Cerium dioxide nanoparticles with a size of 6 nm at a concentration of 0.01 M showed intermediate cytotoxicity, which exceeded control values by 3.5 times, and after the effect of nanoparticles with a size of 2 nm at a concentration of 0.1 M, the cytotoxicity coefficient corresponded to control values. The addition of inactivated blood serum to the incubation mixture resulted in a decreased cytotoxic effect of cerium dioxide. The use of D. viridis as a test system will supplement the arsenal of biotesting tools for nanomaterials and the study of the mechanisms of their effect.


Abbas, F., Jan, Т., Iqbal, J., & Haider, M. S. (2015). Fe doping induced enhancement in room temperature ferromagnetism and selective cytotoxicity of CeO2 nanoparticles. Current Applied Physics, 15(11), 1428–1434.

Babu, K. S., Anandkumar, M., Tsai, T. Y., Kao, T. H., Inbaraj, B. S., & Chen, B. H. (2014). Cytotoxicity and antibacterial activity of gold-supported cerium oxide nanoparticles. International Journal Nanomedicine, 9, 5515–5531.

Bozhkov, A. I., Goltvyanskij, A. V., & Rostama, S. (2010). A primary reaction to stress induced by high copper ion concentration. Algologia, 20(2), 151–166.

Celardo, I., Pedersen, J. Z., Traversa, E., & Ghibelli, L. (2011). Pharmacological potential of cerium oxide nanoparticles. Nanoscale, 3(4), 1411–1420.

Charbgoo, F., Ahmad, M. B., & Darroudi, M. (2017). Cerium oxide nanoparticles: Green synthesis and biological applications. International Journal Nanomedicine, 12, 1401–1413.

Chen, H., & Jiang, J. G. (2009). Osmotic responses of Dunaliella to the changes of salinity. Journal of Cellular Physiology, 219, 251–258.

Cheng, L., Jiang, X., Wang, J., Chen, C., & Liu, R. S. (2013). Nano-bio effects: Interaction of nanomaterials with cells. Nanoscale, 5(9), 3547–3569.

Coleman, R. A. (2011). Efficacy and safety of new medicines: A human focus. Cell Tissue Bank, 12(1), 3–5.

Doak, S. H., Manshian, B., Jenkins, G. J. S., & Singh, N. (2012). In vitro genotoxicity testing strategy for nanomaterials and the adaptation of current OECD guidelines. Mutation Research, 745, 104–111.

Estevez, A. Y., & Erlichman, J. C. (2014). The potential of cerium oxide nanoparticles (nanoceria) for neurodegenerative disease therapy. Nanomedicine, 9, 1437–1440.

Fontes, J. A., Barin, J. G., Talor, M. V., Stickel, N., Schaub, J., Rose, N. R., & Cihakova, D. (2017). Complete Freund’s adjuvant induces experimental autoimmune myocarditis by enhancing IL-6 production during initiation of the immune response. Immunity, Inflammation, Disease, 5(2), 163–176.

Garcia-Saucedo, C., Field, J. A., Otero-Gonzalez, L., & Sierra-Álvarez, R. (2011). Low toxicity of HfO2, SiO2, Al2O3 and CeO2 nanoparticles to the yeast, Saccharomyces cerevisiae. Journal of Hazardous Materials, 192, 1572–1579.

Hexin, L., Xianggan, C., Fazli, W., Feng, X., Cheng, Z., & Shiru, J. (2016). Analysis of the physiological and molecular responses of Dunaliella salina to macronutrient deprivation. PLoS One, 11(3), e0152226.

Hoet, P. H., Bruske-Hohlfeld, I., & Salata, O. V. (2004). Nanoparticles – known and unknown health risks. Journal Nanotechnology, 2(12), 1–15.

Izu, N., Matsubara, I., Itoh, T., Akamatsu, T., & Shin, W. (2013). CO responses of sensors based on cerium oxide thick films prepared from clustered spherical nanoparticles. Sensors (Basel), 13(3), 3252–3261.

Jurado-Sanchez, B. (2018). Microscale and nanoscale biosensors. Biosensors, 8(3), 66.

Klimova, E. M., Bozhkov, A. I., Boyko, V. V., Drozdova, L. A., Lavinskaya, Е. V., & Skok, M. V. (2016). Endogenic cytotoxic compounds and formation of the clinic forms of myasthenia. Translational Biomedicine, 7(3), 1–13.

Kurvet, I., Juganson, K., Vija, H., Sihtmae, M., Blinova, I., Syvertsen-Wiig., G., & Kahru, A. (2017). Toxicity of nine (doped) rare earth metal oxides and respective individual metals to aquatic microorganisms Vibrio fischeri and Tetrahymena thermophile. Materials (Basel), 10(7), 754.

Masjuk, N. P. (1973). Morfologija, sistematika, ekologija, geograficheskoe rasprostranenie roda Dunaliella Teod. i perspektivy ego prakticheskogo ispol’zovanija [Morphology, systematics, ecology, geographical distribution of the genus Dunaliella Teod. and prospects for its practical use]. Naukova Dumka, Kiev (in Russian).

Men’shikov, V. V. (1987). Laboratornye metody issledovanija v klinike [Laboratory research methods in the clinic]. Medicina, Moscow (in Russian).

Minchenko, D. O., Spivak, M. Y., Herasymenko, R. M., Ivanov, V. K., Tretyakov, Y. D., & Minchenko, О. Н. (2013). Effect of cerium dioxide nanoparticles on the expression of selected growth and transcription factors in human astrocytes. Materialwissenschaft und Werkstofftechnik, 44(2–3), 156–160.

Mohs, R. C., & Greig, N. H. (2017). Drug discovery and development: Role of basic biological research. Alzheimers Dement (N Y), 3(4), 651–657.

Nourmohammadi, E., Khoshdel-Sarkazi, H., Nedaeinia, R., Sadeghnia, H. R., Hasanzadeh, L., Darroudi, M., & Kazemi, O. R. (2019). Evaluation of anticancer effects of cerium oxide nanoparticles on mouse fibrosarcoma cell line. Journal of Cellular Physiology, 234(4), 4987–4996.

Prevo, B., Scholey, J. M., & Peterman, E. J. G. (2017). Intraflagellar transport: Mechanisms of motor action, cooperation, and cargo delivery. The FEBS Journal, 284(18), 2905–2931.

Radosevic, K., Radosevic, K., van Leeuwen, A. M. T., Segers-Nolten, G. M. J., Figdor, C., de Grooth, B. G., & Greve, J. (1994). Changes in actin organization during the cytotoxic process. Cytometry, 15(4), 320–326.

Reilein, A. R., Rogers, S. L., Tuma, M. C., & Gelfand, V. I. (2001). Regulation of molecular motor proteins. International Review Cytology, 204, 179–238.

Rostama, S., Bozhkov, A. I., & Goltvyanskiy, A. V. (2012). Effect of copper, lead and cadmium ions on the induction of cells of Dunaliella viridis (Chlorophyta) aggregation. Algologia, 22(1), 30–43.

Sahu, D., Kannan, G. M., Tailang, M., & Vijayaraghavan, R. (2016). In vitro cytotoxicity of nanoparticles: A comparison between particle size and cell type. Journal of Nanoscience, 2016, 1–9.

Schroer, T. A. (1994). Structure, function and regulation of cytoplasmic dynein. Current Opinion in Cell Biology, 6, 69.

Schubert, D., Dargusch, R., Raitano, J., & Chan, S. W. (2006). Cerium and yttrium oxide nanoparticles are neuroprotective. Biochemical and Biophysical Research Communication, 342(1), 86–91.

Sharifi, S., Behzadi, S., Laurent, S., Forrest, M. L., Stroeve, P., & Mahmoudi, M. (2012). Toxicity of nanomaterials. Chemical Society Reviews, 41(6), 2323–2343.

Shcherbakov, A. B., Zholobak, N. M., Baranchikov, A. E., Ryabova, A. V., & Ivanov, V. K. (2015). Cerium fluoride nanoparticles protect cells against oxidative stress. Materials Science and Engineering C, 50, 151–159.

Shi, K., Cui, L., Jiang, H., Yang, L., & Xue, L. (2013). Characterization of the microtubule-binding activity of kinesin-like calmodulin binding protein from Dunaliella salina. Research in Microbiology, 164(10), 1028–1034.

Tomlenovich, L., & Show, C. (2011). Aluminum adjuvants in vaccines. Current Medicinal Chemistry, 18, 2630–2637.

Vale, R. D., & Fletterick, R. J. (1997). The design plan of kinesin motors. Annual Review of Cell and Developmental Biology, 13, 745–777.