Molecular mechanisms of aluminium ions neurotoxicity in brain cells of fish from various pelagic areas

  • E. V. Sukharenko Bingöl University
  • I. V. Samoylova Bingöl University
  • V. S. Nedzvetsky Bingöl University, Oles Honchar Dnipro National University
Keywords: aquatic organisms, oxidative stress, neurospecific proteins, glial fibrillary acidic protein, GFAP, protein S100β


Neurotoxic effects of aluminum chloride in higher than usual environment concentration (10 mg/L) were studied in brains of fishes from various pelagic areas, especially in sunfish (Lepomis macrochirus Rafinesque, 1819), roach (Rutilus rutilus Linnaeus, 1758), crucian carp (Carasius carasius Linnaeus, 1758), goby (Neogobius fluviatilis Pallas, 1811). The intensity of oxidative stress and the content of both cytoskeleton protein GFAP and cytosol Ca-binding protein S100β were determined. The differences in oxidative stress data were observed in the liver and brain of fish during 45 days of treatment with aluminum chloride. The data indicated that in the modeling of aluminum intoxication in mature adult fishes the level of oxidative stress was noticeably higher in the brain than in the liver. This index was lower by1.5–2.0 times on average in the liver cells than in the brain. The obtained data evidently demonstrate high sensitivity to aluminum ions in neural tissue cells of fish from various pelagic areas. Chronic intoxication with aluminum ions induced intense astrogliosis in the fish brain. Astrogliosis was determined as result of overexpression of both cytoskeleton and cytosole markers of astrocytes – GFAP and protein S100β (on 75–112% and 67–105% accordingly). Moreover, it was shown that the neurotixic effect of aluminum ions is closely related to metabolism of astroglial intermediate filaments. The results of western blotting showed a considerable increase in the content of the lysis protein products of GFAP with a range of molecular weight from 40–49 kDa. A similar metabolic disturbance was determined for the upregulation protein S100β expression and particularly in the increase in the content of polypeptide fragments of this protein with molecular weight 24–37 kDa. Thus, the obtained results allow one to presume that aluminum ions activate in the fish brain intracellular proteases which have a capacity to destroy the proteins of intermediate filaments. The data presented display the pronounced neurotoxic effect of mobile forms of aluminum on both expression level and the metabolism of molecular markers of astrocytes GFAP and protein S100β. Aluminum ions induce integrated changes, the more important of which are a significant increase in final LPO products, an increase in antioxidant enzyme activity, a reactivation of glial cells in the brain. Integrated determination of the content and polypeptide fragments of specific astrocyte proteins in fishes brains coupled with oxidative stress data may be used as valid biomarkers of toxic pollutant effects in aquatic environments.


Aksu, A. J. (2015). Sources of metal pollution in the urban atmosphere (A case study: Tuzla, Istabul). Journal of Environmental Health Science and Engine ering, 13, 79.
Ben Haim, L., Carrillo-de Sauvage, M. A., Ceyzériat, K., & Escartin, C. (2015). Elusive roles for reactive astrocytes in neurodegenerative diseases. Frontiers in Cellular Neuroscience, 9, 278.
Cardwell, A. S., Adams, W. J., Gensemer, R. W., Nordheim, E., Santore, R. C., Ryan, A. C., & Stubblefield, W. A. (2017). Chronic toxicity of aluminum, at a pH of 6, to freshwater organisms: Empirical data for the development of international regulatory standards/criteria. Environmental Toxicology and Chemistry, in print.
Driscoll, C. T. (1985). Aluminum in acidic surface waters: Chemistry, transport, and effects. Environmental Health Perspectives, 63, 93–104.
Eng, L. F, Ghirnikar, R. S., & Lee, Y. L. (2000). Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochemical Research, 25(9–10), 1439–1451.
Fernandez-Davila, M. L., Razo-Estrada, A. C., García-Medina, S., Gomez-Olivan, L. M., Pinon-Lopez, M. J., Ibarra, R. G., & Galar-Martinez, M. (2012). Aluminum-induced oxidative stress and neurotoxicity in grass carp (Cyprinidae – Ctenopharingodon idella). Ecotoxicology and Environmental Safety, 76(2), 87–92.
Garcia-Medina, S., Razo-Estrada, C., Galar-Martinez, M., Cortez-Barberena, E., Gomez-Olivan, L. M., Alvarez-Gonzalez, I., & Madrigal-Bujaidar, E. (2011). Genotoxic and cytotoxic effects induced by aluminum in the lymphocytes of the common carp (Cyprinus carpio). Comparative Biochemistry and Physiology C: Toxicology and Pharmacology, 153(1), 113–118.
Gillmore, M. L., Golding, L. A., Angel, B. M., Adams, M. S., & Jolley, D. F. (2016). Toxicity of dissolved and precipitated aluminium to marine diatoms. Aquatic Toxicology, 174, 82–91.
Gostomski, F. (1990). The toxicity of aluminum to aquatic species in the US. Environ Chemistry Health, 12(1–2), 51–54.
Grassie, C., Braithwaite, V. A., Nilsson, J., Nilsen, T. O., Teien, H. C., Handeland, S. O., Stefansson, S. O., Tronci, V., Gorissen, M., Flik, G., & Ebbesson, L. O. (2013). Aluminum exposure impacts brain plasticity and behavior in Atlantic salmon (Salmo salar). Experimental Biology, 216(16), 3148–3155.
Grassie, C., Braithwaite, V. A., Nilsson, J., Nilsen, T. O., Teien, H. C., Handeland, S. O., Stefansson, S. O., Tronci, V., Gorissen, M., Flik, G., & Ebbesson, L. O. (2013). Aluminum exposure impacts brain plasticity and behavior in Atlantic salmon (Salmo salar). Journal of Experimental Biology, 216(16), 3148–3155.
Liu, S., Noth, E. M, Dixon-Ernst, C., Eisen, E. A, Cullen, M. R, & Hammond, S. K. (2014). Particle size distribution in aluminum manufacturing facili ties. Environmental Pollution, 4(3), 79–88.
Miller, G. L. (1959). Protein determination for large numbers of samples, Analyti cal Chemistry, 31(5), 964–966.
Nedzvetskii, V. S., Kirichenko, S. V., Baydas, G., & Nerush, O. P. (2012). Effects of melatonin on memory and learning deficits induced by exposure to thinner. Neurophysiology/Neirofiziologiya, 44(1), 42–48.
Nedzvetskii, V. S., Tuzcu, M., Yasar, A., Tikhomirov, A. A., & Baydas, G. (2006). Effects of vitamin E against aluminum neurotoxisity in rats. Biochemistry (Moscow), 71(3), 239–244.
Nedzvetskiy, V. S., & Nerush, P. O. (2011). Hyperthyreosis effects on the learning, memory and glial intermediate filaments of a rat brain. Physiology and Pathophysiology, 2, 269–278.
Nedzvetsky, V. S., Ushakova, G. A., Busigina, S. G., Berezin, V. A., & Dvoret sky, A. I. (1991). Effect of low-level radiation on intermediate filaments and Ca-activated proteolysis in rat brain. Radiobiology (Moscow), 31(3), 333–339.
Ohkawa, H. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351–358.
Pereira, S., Cavalie, I., Camilleri, V., Gilbin, R., & Adam-Guillermin, C. (2013). Comparative genotoxicity of aluminium and cadmium in embryonic zebra fish cells. Mutation Research, 750(1–2), 19–26.
Singla, N., & Dhawan, D. K. (2015). Modulation of (14) C-labeled glucose meta bolism by zinc during aluminium induced neurodegeneration. Neuroscience Research, 93(9), 1434–1441.
Sivakumar, S., Khatiwada, C. P., & Sivasubramanian, J. (2012). Bioaccumulations of aluminum and the effects of chelating agents on different organs of Cirrhinus mrigala. Environtal Toxicology and Pharmacology, 34(3), 791–800.
Skilbrei, O. T., Finstad, B., Urdal, K., Bakke, G., Kroglund, F., & Strand, R. (2013). Impact of early salmon louse, Lepeophtheirus salmonis, infestation and differences in survival and marine growth of sea-ranched Atlantic salmon, Salmo salar L., smolts 1997–2009. Fish Diseases, 36(3), 249–260.
Sukharenko, E. V., Nedzvetsky, V. S., & Kyrychenko, S. V. (2017). Biomarkers of metabolism disturbance in bivalve molluscs induced by environmental pollution with processed by-products of oil. Biosystems Diversity, 25(2), 113–118.
Sun, J. J., Liu, Y., & Ye, Z. R. (2008). Effects of P2Y1 receptor on glial fibrilla ry acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways. Neuroscience Bulletin, 24(4), 231–243.
Suzuki, T., Sakata, H., Kato, C., Connor, J. A., & Morita, M. (2012). Astrocyte activation and wound healing in intact-skull mouse after focal brain injury. European Journal of Neuroscience, 36(12), 3653–3664.
Trenfield, M. A., Markich, S. J., Ng, J. C., Noller, B., & van Dam, R. A. (2012). Dissolved organic carbon reduces the toxicity of aluminum to three tropical freshwater organisms. Environmental Toxicology and Chemistry, 31(2), 427–436.
Tykhomyrov, A. A., Pavlova, A. S., & Nedzvetsky, V. S. (2016). Glial fibrillary acidic protein (GFAP): On the 45th anniversary of discovery. Neurophysio logy (Springer), 48(1), 54–71.
Walton, R. C., McCrohan, C. R., Livens, F., & White, K. N. (2010). Trophic transfer of aluminium through an aquatic grazer-omnivore food chain. Aquatic Toxicology, 99(1), 93–99.
How to Cite
Sukharenko, E., Samoylova, I., & Nedzvetsky, V. (2017). Molecular mechanisms of aluminium ions neurotoxicity in brain cells of fish from various pelagic areas. Regulatory Mechanisms in Biosystems, 8(3), 461-466.

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