Indices of the DNA repair system in the brain of fish as a biomarker of inorganic mercury burden

  • V. S. Nedzvetsky Bingöl University, Bingöl, Turkey
  • V. Ya. Gasso Oles Honchar Dnipro National University, Dnipro, Ukraine
  • R. O. Novitskyi Dnipro State Agrarian and Economic University, Dnipro, Ukraine
  • I. A. Hasso Oles Honchar Dnipro National University, Dnipro, Ukraine
Keywords: rainbow trout, Oncorhynchus mykiss, heavy metal, oxidative stress, reactive oxygen species, ROS, ERCC, PARP

Abstract

Mercury is a widespread heavy metal that causes a stable and prolonged environmental pollution. Low concentrations of inorganic and organic mercury compounds are found in almost all water bodies. The high level of mercury bioaccumulation is a cause of tissue-specific toxicity, including neurotoxicity. Absorbed in nervous tissue mercury can cause brain disorders both in neural and glial cells. The brain of fish is considered one of the most susceptible targets for cytotoxicity of mercury in aquatic ecosystems. Taking into account that different forms of mercury have widespread distribution and exhibit a strong neurotoxic effect, the assessment of mercury cytotoxicity in the brain of fish is relevant and extremely important. Rainbow trout Oncorhynchus mykiss was exposed to mercury chloride in the dose range of 5-20 μg/L for 60 days to study the chronic exposure of low doses. In this paper, we studied the influence of inorganic mercury on oxidative stress, DNA repair proteins – ERCC1 and PARP1 in the trout’s brain. The results obtained have shown that the chronic effect of inorganic mercury causes dose-dependent oxidative stress in the fish brain. In addition, low concentrations of mercury (10 and 20 μg/L) caused a decrease in the content of ERCC1 in the brain of fish. On the contrary, the same doses have caused an increase in PARP1 expression. That is the chronic influence of low concentrations of inorganic mercury has a negative effect in the fish brain. Observed results showed that inorganic mercury has a potential for suppressing DNA repair and, therefore, increases the instability of genome. Thus, ERCC1 and PARP1 can be considered as the sensitive biomarkers of mercury cytotoxicity in the fish brain. A further study of mercury neurotoxicity is needed to find out the hazard of mercury environmental pollution as well as a validation of biomarkers of their impact.

References

Amlund, H., Lundebye, A. K., Berntssen, M. H. (2007). Accumulation and elimination of methylmercury in Atlantic cod (Gadus morhua L.) following dietary exposure. Aquatic Toxicology, 83(4), 323–330.



Aschner, M., Aschner, J. L. (1990). Mercury neurotoxicity: mechanisms of blood-brain barrier transport. Neuroscience and Biobehavioral Reviews, 14(2), 169–176.



Bagchi, D., Bagchi, M., Stohs, S. J. (2001). Chromium (VI)-induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene. Molecular and Cellular Biochemistry, 222(1-2), 149–158.



Bai P. (2015). Biology of poly(ADP-Ribose) polymerases: The factotums of cell maintenance. Molecular Cell, 58(6), 947–958.



Biswas S., Bellare J. Adaptive mechanisms induced by sparingly soluble mercury sulfide (HgS) in zebrafish: Behavioural and proteomics analysis. Chemosphere, 2021, 270, 129438. 



Bock, F. J., Chang, P. (2016). New directions in poly(ADP-ribose) polymerase biology. FEBS Journal, 283(22), 4017–4031.



Brandão, F., Cappello, T., Raimundo, J., Santos, M.A., Maisano, M., Mauceri, A., Pacheco, M., Pereira, P. (2015). Unravelling the mechanisms of mercury hepatotoxicity in wild fish (Liza aurata) through a triad approach: bioaccumulation, metabolomic profiles and oxidative stress. Metallomics: integrated biometal science, 7(9), 1352–1363.



Cariccio, V. L., Samà, A., Bramanti, P., Mazzon, E. (2019). Mercury involvement in neuronal damage and in neurodegenerative diseases. Biological Trace Element Research, 187(2), 341–356.



Carocci, A., Rovito, N., Sinicropi, M.S., Genchi, G. (2014). Mercury toxicity and neurodegenerative effects. Rev Environ Contam Toxicol., 229, 1–18.



Chang, Y., Lee, W.Y., Lin, Y.J., Hsu, T. (2017). Mercury (II) impairs nucleotide excision repair (NER) in zebrafish (Danio rerio) embryos by targeting primarily at the stage of DNA incision. Aquatic Toxicology, 192, 97–104.



Ciardullo, S., Aureli, F., Coni, E., Guandalini, E., Iosi, F., Raggi, A., Rufo, G., Cubadda, F. (2008). Bioaccumulation potential of dietary arsenic, cadmium, lead, mercury, and selenium in organs and tissues of rainbow trout (Oncorhyncus mykiss) as a function of fish growth. Journal of Agricultural and Food Chemistry, 56(7), 2442–2451.



Dos Santos, A. A., Ferrer, B., Marques Gonçalves, F., Tsatsakis, A. M., Renieri, E. A., Skalny, A. V., Farina, M., Rocha, J., Aschner, M. (2018). Oxidative stress in methylmercury-induced cell toxicity. Toxics, 6(3), 47.



Eagles-Smith, C. A., Ackerman, J. T., Willacker, J. J., Tate, M. T., Lutz, M. A., Fleck, J. A., Stewart, A. R., Wiener, J. G., Evers, D. C., Lepak, J. M., Davis, J. A., Pritz, C. F. (2016a). Spatial and temporal patterns of mercury concentrations in freshwater fish across the Western United States and Canada. Science of the Total Environment, 15(568), 1171–1184.



Eagles-Smith, C. A., Wiener, J. G., Eckley, C. S., Willacker, J. J., Evers, D. C., Marvin-DiPasquale, M., Obrist, D., Fleck, J. A., Aiken, G. R., Lepak, J. M., Jackson, A. K., Webster, J. P., Stewart, A. R., Davis, J. A., Alpers, C. N., Ackerman, J. T. (2016b). Mercury in western North America: A synthesis of environmental contamination, fluxes, bioaccumulation, and risk to fish and wildlife. Science of the Total Environment, 15(568), 1213–1226.



García-Medina, S., Galar-Martínez, M., Gómez-Oliván, L. M., Ruiz-Lara, K., Islas-Flores, H., & Gasca-Pérez, E. (2017). Relationship between genotoxicity and oxidative stress induced by mercury on common carp (Cyprinus carpio) tissues. Aquatic Toxicology, 192, 207–215.



Gasso V. Y., Hahut A. N., Yermolenko S. V., Hasso, I. A., Agca, C. A., Nedzvetsky, V. S., Sukharenko E. V. (2020). Local industrial pollution induces astrocyte cytoskeleton rearrangement in the dice snake brain: GFAP as a biomarker. Biosystems Diversity, 28(3), 250–256.



Giblin, F. J., Massaro, E. J. (1975). The erythrocyte transport and transfer of methylmercury to the tissues of the rainbow trout (Salmo gairdneri). Toxicology, 5, 243–254.



Gómez-Oliván, L. M., Mendoza-Zenil, Y. P., SanJuan-Reyes, N., Galar-Martínez, M., Ramírez-Durán, N., Rodríguez Martín-Doimeadios, R., Rodríguez-Fariñas, N., Islas-Flores, H., Elizalde-Velázquez, A., García-Medina, S., Pérez-Pastén Borja, R. (2017). Geno- and cytotoxicity induced on Cyprinus carpio by aluminum, iron, mercury and mixture thereof. Ecotoxicology and environmental safety, 135, 98–105.



Harayashiki, C., Reichelt-Brushett, A., Benkendorff, K. (2019). Behavioural and brain biomarker responses in yellowfin bream (Acanthopagrus australis) after inorganic mercury ingestion. Marine Environmental Research, 144, 62–71.



Has-Schön, E., Bogut, I., Vuković, R., Galović, D., Bogut, A., Horvatić, J. (2015). Distribution and age-related bioaccumulation of lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) in tissues of common carp (Cyprinus carpio) and European catfish (Sylurus glanis) from the Buško Blato reservoir (Bosnia and Herzegovina). Chemosphere, 135, 289–296.



Horowitz, H. M., Jacob, D. J., Amos, H. M., Streets, D. G., Sunderland, E. M. (2014). Historical mercury releases from commercial products: global environmental implications. Environmental Science and Technology, 48(17), 10242–10250.



Hussain, B., Sultana, T., Sultana, S., Masoud, M. S., Ahmed, Z., Mahboob, S. (2018). Fish eco-genotoxicology: Comet and micronucleus assay in fish erythrocytes as in situ biomarker of freshwater pollution. Saudi Journal of Biological Sciences, 25(2), 393–398.



Kenšová, R., Kružíková, K., Havránek, J, Haruštiaková, D, Svobodová, Z. (2012). Distribution of mercury in rainbow trout tissues at embryo-larval and juvenile stages. Scientific World Journal, 2012, 652496.



Kirici, M., Nedzvetsky, V. S., Agca, C. A., Gasso, V. Y. (2019). Sublethal doses of copper sulphate initiate deregulation of glial cytoskeleton, NF-kB and PARP expression in Capoeta umbla brain tissue. Regulatory Mechanisms in Biosystems, 10 (1), 103-110.



Koutsoukos, K., Andrikopoulou, A., Dedes, N., Zagouri, F., Bamias, A., Dimopoulos, M. A. (2020). Clinical Perspectives of ERCC1 in Bladder Cancer. International Journal of Molecular Sciences, 21(22), 8829.



Leonard, S. S., Harris, G. K., Shi, X. (2004). Metal-induced oxidative stress and signal transduction. Free Radical Biology and Medicine, 37(12), 1921–1942.



Lin, X., Zhao, J., Zhang, W., He, L., Wang, L., Li, H., Liu, Q., Cui, L., Gao, Y., Chen, C., Li, B., Li, Y. F. (2021). Towards screening the neurotoxicity of chemicals through feces after exposure to methylmercury or inorganic mercury in rats: A combined study using gut microbiome, metabolomics and metallomics. Journal of Hazardous Materials, 409, 124923.



Liu, Q., Basu, N., Goetz, G., Jiang, N., Hutz, R. J., Tonellato, P. J., Carvan, M. J., 3rd. (2013). Differential gene expression associated with dietary methylmercury (MeHg) exposure in rainbow trout (Oncorhynchus mykiss) and zebrafish (Danio rerio). Ecotoxicology, 22(4), 740–751.



Lohren, H., Blagojevic, L., Fitkau, R., Ebert, F., Schildknecht, S., Leist, M., Schwerdtle, T. (2015). Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes. Journal of Trace Elements in Medicine and Biology, 32, 200–208.



Lohren, H., Bornhorst, J., Fitkau, R., Pohl, G., Galla, H. J., Schwerdtle, T. (2016). Effects on and transfer across the blood-brain barrier in vitro – Comparison of organic and inorganic mercury species. BMC Pharmacology and Toxicology, 17(1), 63.



Manceau, A., Bourdineaud, J.-P., Oliveira, R. B., Sarrazin, S. L. F., Krabbenhoft, D. P., Eagles-Smith, C. A., Ackerman, J. T., Stewart, A. R., Ward-Deitrich, C., del Castillo Busto, M. E., Goenaga-Infante, H., Wack, A., Retegan, M., Detlefs, B., Glatzel, P., Bustamante, P., Nagy, K. L., Poulin, B. A. (2021). Demethylation of methylmercury in bird, fish, and earthworm. Environmental Science and Technology, 55, 1527-1534.



Meena, R., Sathishkumar, P., Ameen, F., Yusoff, A., Gu, F. L. (2018). Heavy metal pollution in immobile and mobile components of lentic ecosystems-a review. Environmental Science and Pollution Research International, 25(5), 4134–4148.



Mieiro, C. L., Pacheco, M., Pereira, M. E., Duarte, A. C. (2011). Mercury organotropism in feral European sea bass (Dicentrarchus labrax). Archives of Environmental Contamination and Toxicology, 61(1), 135–143.



Naïja, A., Kestemont, P., Chénais, B., Haouas, Z., Blust, R., Helal, A. N., Marchand, J. (2018). Effects of Hg sublethal exposure in the brain of peacock blennies Salaria pavo: Molecular, Physiological and Histopathological Analysis. Chemosphere, 193, 1094–1104.



Nedzvetsky, V. S., Gasso, V. Ya., Hahut, A. M., Hasso, I. A. (2020b). Influence of cadmium contamination on brain glial cells: consequences and bioindication possibilities. Issues of Steppe Forestry and Forest Reclamation of Soils, 49, 68–83 (in Ukrainian).



Nedzvetsky, V. S., Gasso, V. Ya., Hahut, A. M., Hasso, I. A. (2020a). Glial cytotoxicity of low doses of cadmium as a model of heavy metal pollution influence on vertebrates. Ecology and Noospherology, 31(1), 3–10 (in Ukrainian).



Obrist, D., Kirk, J. L., Zhang, L., Sunderland, E. M., Jiskra, M., Selin, N. E. (2018). A review of global environmental mercury processes in response to human and natural perturbations: Changes of emissions, climate, and land use. Ambio, 47(2), 116–140.



Ohgoh, M., Shimizu, H., Ogura, H., Nishizawa, Y. (2000). Astroglial trophic support and neuronal cell death: influence of cellular energy level on type of cell death induced by mitochondrial toxin in cultured rat cortical neurons. Journal of Neurochemistry, 75, 925–933.



Orihel, D. M., Paterson, M. J., Blanchfield, P. J., Bodaly, R. A., Hintelmann, H. (2007). Experimental evidence of a linear relationship between inorganic mercury loading and methylmercury accumulation by aquatic biota. Environmental Science and Technology, 41(14), 4952–4958.



Pereira, C. S., Guilherme, S. I., Barroso, C. M., Verschaeve, L., Pacheco, M. G., Mendo, S. A. (2010). Evaluation of DNA damage induced by environmental exposure to mercury in Liza aurata using the comet assay. Archives of Environmental Contamination and Toxicology, 58(1), 112–122.



Pereira, P., Korbas, M., Pereira, V., Cappello, T., Maisano, M., Canário, J., Almeida, A., Pacheco, M. (2019). A multidimensional concept for mercury neuronal and sensory toxicity in fish - From toxicokinetics and biochemistry to morphometry and behavior. Biochimica et Biophysica Acta. General subjects, 1863(12), 129298.



Pereira, P., Puga, S., Cardoso, V., Pinto-Ribeiro, F., Raimundo, J., Barata, M., Pousão-Ferreira, P., Pacheco, M., Almeida, A. (2016). Inorganic mercury accumulation in brain following waterborne exposure elicits a deficit on the number of brain cells and impairs swimming behavior in fish (white seabream - Diplodus sargus). Aquatic Toxicology, 170, 400–412.



Pereira, P., Raimundo, J., Araújo, O., Canário, J., Almeida, A., Pacheco, M. (2014). Fish eyes and brain as primary targets for mercury accumulation - a new insight on environmental risk assessment. The Science of the Total Environment, 494-495, 290–298.



Pereira, P., Raimundo, J., Barata, M., Araújo, O., Pousão-Ferreira, P., Canário, J., Almeida, A., Pacheco, M. (2015). A new page on the road book of inorganic mercury in fish body - tissue distribution and elimination following waterborne exposure and post-exposure periods. Metallomics: integrated biometal science, 7(3), 525–535.



Pickhardt P.C., Stepanova M., Fisher N.S., Contrasting uptake routes and tissue distributions of inorganic and methylmercury in mosquito fish (Gambusia affinis) and redear sunfish (Lepomis microlophus), Environmental Toxicology and Chemistry. 25 (2006) 2132–2142.



Pillet, M., Castaldo, G., De Weggheleire, S., Bervoets, L., Blust, R., De Boeck, G. (2019). Limited oxidative stress in common carp (Cyprinus carpio, L., 1758) exposed to a sublethal tertiary (Cu, Cd and Zn) metal mixture. Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP, 218, 70–80.



Pletz, J., Sánchez-Bayo, F., Tennekes, H. A. (2016). Dose-response analysis indicating time-dependent neurotoxicity caused by organic and inorganic mercury – Implications for toxic effects in the developing brain. Toxicology, 347-349, 1–5.



Santovito, G., Piccinni, E., Boldrin, F., Irato, P. (2012). Comparative study on metal homeostasis and detoxification in two Antarctic teleosts. Comparative biochemistry and physiology. Toxicology & Pharmacology: CBP, 155(4), 580–586.



Sevcikova, M., Modra, H., Blahova, J., Dobsikova, R., Kalina, J., Zitka, O., Kizek, R., Svobodova, Z. (2015). Factors affecting antioxidant response in fish from a long-term mercury-contaminated reservoir. Archives of Environmental Contamination and Toxicology, 69(4), 431–439.



Simmons S. O., Fan C. Y., Yeoman K., Wakefield J., Ramabhadran R. (2011). NRF2 oxidative stress induced by heavy metals is cell type dependent. Current Chemical Genomics, 5, 1–12.



Simon, O., Boudou, A. (2001). Direct and trophic contamination of the herbivorous carp Ctenopharyngodon idella by inorganic mercury and methylmercury. Ecotoxicology and Environmental Safety, 50(1), 48–59.



Szunyogh, D., Gyurcsik, B., Larsen, F. H., Stachura, M., Thulstrup, P. W., Hemmingsen, L., Jancsу, A. (2015). Zn(II) and Hg(II) binding to a designed peptide that accommodates different coordination geometries. Dalton Transactions, 44(28), 12576–12588.



Takahashi, T., Fujimura, M., Koyama, M., Kanazawa, M., Usuki, F., Nishizawa, M., Shimohata, T. 2017. Methylmercury causes blood-brain barrier damage in rats via upregulation of vascular endothelial growth factor expression. PLoS ONE, 12(1): e0170623.



Taysi, M. R., Sogut, D., Nedzvetsky, V. S., Kirici, M., Agca, C. A. (2019). Sublethal doses of inorganic mercury induce dose-dependent upregulation of RPA1 content and inhibit p53 expression in the brain of rainbow trout (Oncorhynchus mykiss). Turkish Journal of Agricultural and Natural Sciences, 6(3), 462–476.



Toimela, T., Mäenpää, H., Mannerström, M., Tähti, H. (2004). Development of an in vitro blood-brain barrier model-cytotoxicity of mercury and aluminum. Toxicology and Applied Pharmacology, 195(1), 73–82.



Valavanidis, A., Vlahogianni, T., Dassenakis, M., Scoullos, M. (2006). Molecular biomarkers of oxidative stress in aquatic organisms in relation to toxic environmental pollutants. Ecotoxicology and Environmental Safety, 64(2), 178–189.



van der Oost, R., Beyer, J., Vermeulen, N. P. (2003). Fish bioaccumulation and biomarkers in environmental risk assessment: a review. Environmental Toxicology and Pharmacology, 13(2), 57–149.



van Rensburg, M. J., van Rooy, M., Bester, M. J., Serem, J. C., Venter, C., Oberholzer, H. M. (2019). Oxidative and haemostatic effects of copper, manganese and mercury, alone and in combination at physiologically relevant levels: An ex vivo study. Human & Experimental Toxicology, 38(4), 419–433.



Vieira, L. R., Gravato, C., Soares, A. M., Morgado, F., Guilhermino, L. (2009). Acute effects of copper and mercury on the estuarine fish Pomatoschistus microps: linking biomarkers to behaviour. Chemosphere, 76(10), 1416–1427.



Wang, W-X., Wong, R. S. K. (2003). Bioaccumulation kinetics and exposure pathways of inorganic mercury and methylmercury in a marine fish, the sweetlips Plectorhinchus gibbosus. Marine Ecology Progress Series, 261, 257–268.



Wang, X., Wu, F., Wang, W. X. (2017). In vivo mercury demethylation in a marine fish (Acanthopagrus schlegeli). Environmental Science and Technology, 51(11), 6441–6451.



Wang, Y., Wang, D., Lin, L., Wang, M. (2015). Quantitative proteomic analysis reveals proteins involved in the neurotoxicity of marine medaka Oryzias melastigma chronically exposed to inorganic mercury. Chemosphere, 119, 1126–1133.



Wyatt, L. H., Luz, A. L., Cao, X., Maurer, L. L., Blawas, A. M., Aballay, A., Pan, W. K., Meyer, J. N. (2017). Effects of methyl and inorganic mercury exposure on genome homeostasis and mitochondrial function in Caenorhabditis elegans. DNA repair, 52, 31–48.



Yang, T. T., Liu, Y., Tan, S., Wang, W. X., Wang, X. (2021). The role of intestinal microbiota of the marine fish (Acanthopagrus latus) in mercury biotransformation. Environmental Pollution, 277, 116768.



Zheng, W., Aschner, M., Ghersi-Egea, J. F. (2003). Brain barrier systems: a new frontier in metal neurotoxicological research. Toxicology and Applied Pharmacology, 192(1), 1–11.


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Published
2021-05-22
How to Cite
Nedzvetsky, V., Gasso, V., Novitskyi, R., & Hasso, I. (2021). Indices of the DNA repair system in the brain of fish as a biomarker of inorganic mercury burden. Ecology and Noospherology, 32(1), 9-16. https://doi.org/https://doi.org/10.15421/032102