• Olena Kuzenko Kharkiv Medical Academy of Postgraduate Education
  • Yuri Demin Kharkiv Medical Academy of Postgraduate Education
  • Yevhen Kuzenko Medical Institute of Sumy State University
Keywords: chromium-induced neuropathy, oxidative stress, heat shock proteins, global pollution


Intoxication lesions of the optic nerve (toxic optic neuropathy, TON) most often occur under the influence of exogenous factors, including heavy metals. Сell survival under stress have involves heat shock proteins (HSPs).

The aim of the research. To assess the optic nerve’s immunoreactivity to heat shock proteins of the HSP70 and HSP90α families and reveal its relationship with the severity of morphological changes in toxic optic neuropathy caused by Cr (VI).

Materials and methods. The study was conducted on 48 mature male rats. The experimental groups were given to drink water with Cr(VI) for 20, 40 and 60 days. This type of water is typical for the water basins in the northern districts of the Sumy region. Optic nerves сhanges under the influence of Cr(VI) have investigated by the morphometric method. Neuroglial cells and capillary endothelial cells were assessed by immunohistochemistry by HSP70α and HSP90 expression for intensity and spatial distribution.

Results. The data analysis revealed that Cr (VI) has a neurotoxic effect on the optic nerve with the development of edema, which is manifested by the thickening of nerve fibers. The dynamics of HSP70 immunoexpression in the endothelium of the optic nerve capillaries of rats on 20 and 40 experimental days was characterized by stable values and was 1.5 times higher than the control. The maximum number of positively stained cells for the HSP70 marker was detected in endothelial cells of the microvasculature for 60 days – 82.44±12.42 %. HSP70 levels in neuroglia cells of optic nerve have decreased on day 40 (55.66±11.56% p=0.05) and lower than the control (70.44±4.81 %.) group. Optic nerve capillaries was highest immunoactivity on HSP90 in group II endothelial cells – 51.22±14.57% (p=0.05). The activity of HSP90α protein in optic neuroglia cells was characterized by a gradual increase in the duration of the experiment and was higher by 12, 4 % in experimental group III (81.77±21.67 %) compared with control (71.66±4.95 %).

Conclusions. Our study provides an insight into the significant difference in the immunoreactivity of heat shock proteins of the HSP70 and HSP90α families in neuroglia and endothelial cells of the optic nerve capillaries under the influence of Cr(VI).

The results obtained suggest that Cr (VI) has a neurotoxic effect on the optic nerve with the development of edema, which is manifested by the thickening of nerve fibers. A comparison of the dynamics of the development of the dystrophic process in the optic nerve with the results of the immunohistochemical analysis showed, that an increase in the thickness of nerve fibers is accompanied by an increase in immunoreactive neuroglial cells (HSP90α) and endothelial cells (HSP70).


Download data is not yet available.

Author Biographies

Olena Kuzenko, Kharkiv Medical Academy of Postgraduate Education

Department of Ophthalmology

Yuri Demin, Kharkiv Medical Academy of Postgraduate Education

Department of Ophthalmology

Yevhen Kuzenko, Medical Institute of Sumy State University

Department of Pathology


Kesler, A, Pianka, P. (2003). Toxic optic neuropathy. Current Neurology and Neuroscience Reports, 3 (5), 410–414. doi: DOI:

Sharma, R., Sharma, P. (2011). Toxic optic neuropathy. Indian Journal of Ophthalmology, 59 (2), 137–141. doi: DOI:

Abri Aghdam, K., Zand, A., Soltan Sanjari, M. (2019). Bilateral Optic Disc Edema in a Patient with Lead Poisoning. Journal of ophthalmic & vision research, 14 (4), 513–517. doi: DOI:

Tong, S., Li, H., Wang, L., Tudi, M., Yang, L. (2020). Concentration, Spatial Distribution, Contamination Degree and Human Health Risk Assessment of Heavy Metals in Urban Soils across China between 2003 and 2019 – A Systematic Review. International Journal of Environmental Research and Public Health, 17 (9), 3099. doi: DOI:

Tytła, M. (2019). Assessment of Heavy Metal Pollution and Potential Ecological Risk in Sewage Sludge from Municipal Wastewater Treatment Plant Located in the Most Industrialized Region in Poland – Case Study. International Journal of Environmental Research and Public Health, 16 (13), 2430. doi: DOI:

Sharma, P., Bihari, V., Agarwal, S. K., Verma, V., Kesavachandran, C. N., Pangtey, B. S. et. al. (2012). Groundwater Contaminated with Hexavalent Chromium [Cr (VI)]: A Health Survey and Clinical Examination of Community Inhabitants (Kanpur, India). PLoS ONE, 7 (10), e47877. doi: DOI:

Megremi, I., Vasilatos, C., Vassilakis, E., Economou-Eliopoulos, M. (2019). Spatial diversity of Cr distribution in soil and groundwater sites in relation with land use management in a Mediterranean region: The case of C. Evia and Assopos-Thiva Basins, Greece. Science of The Total Environment, 651, 656–667. doi: DOI:

Doorn, P. F., Campbell, P. A., Worrall, J., Benya, P. D., McKellop, H. A., Amstutz, H. C. (1998). Metal wear particle characterization from metal on metal total hip replacements: transmission electron microscopy study of periprosthetic tissues and isolated particles. Journal of Biomedical Materials Research, 42 (1), 103–111. doi:<103::aid-jbm13>;2-m DOI:<103::AID-JBM13>3.0.CO;2-M

Catelas, I., Bobyn, J. D., Medley, J. B., Krygier, J. J., Zukor, D. J., Huk, O. L. (2003). Size, shape, and composition of wear particles from metal-metal hip simulator testing: Effects of alloy and number of loading cycles. Journal of Biomedical Materials Research, 67A (1), 312–327. doi: DOI:

Mahendra, G., Pandit, H., Kliskey, K., Murray, D., Gill, H. S., Athanasou, N. (2009). Necrotic and inflammatory changes in metal-on-metal resurfacing hip arthroplasties. Acta Orthopaedica, 80 (6), 653–659. doi: DOI:

Korovessis, P., Petsinis, G., Repanti, M., Repantis, T. (2006). Metallosis After Contemporary Metal-on-Metal Total Hip Arthroplasty. The Journal of Bone & Joint Surgery, 88 (6), 1183–1191. doi: DOI:

Campbell, J. R., Estey, M. P. (2013). Metal release from hip prostheses: cobalt and chromium toxicity and the role of the clinical laboratory. Clinical Chemistry and Laboratory Medicine, 51 (1), 213–220. doi: DOI:

Mabilleau, G., Kwon, Y.-M., Pandit, H., Murray, D. W., Sabokbar, A. (2008). Metal-on-metal hip resurfacing arthroplasty: A review of periprosthetic biological reactions. Acta Orthopaedica, 79 (6), 734–747. doi: DOI:

Iavicoli, I., Falcone, G., Alessandrelli, M., Cresti, R., De Santis, V., Salvatori, S. et. al. (2006). The release of metals from metal-on-metal surface arthroplasty of the hip. Journal of Trace Elements in Medicine and Biology, 20 (1), 25–31. doi: DOI:

Apel, W., Stark, D., Stark, A., O’Hagan, S., Ling, J. (2012). Cobalt–chromium toxic retinopathy case study. Documenta Ophthalmologica, 126 (1), 69–78. doi: DOI:

Ng, S., Ebneter, A., Gilhotra, J. (2013). Hip-implant related chorio-retinal cobalt toxicity. Indian Journal of Ophthalmology, 61 (1), 35–37. doi: DOI:

Garcia, M. D., Hur, M., Chen, J. J., Bhatti, M. T. (2020). Cobalt toxic optic neuropathy and retinopathy: Case report and review of the literature. American Journal of Ophthalmology Case Reports, 17, 100606. doi: DOI:

Liu, H., Chen, H., Jing, J., Ma, X. (2011). Cloning and characterization of the HSP90 beta gene from Tanichthys albonubes Lin (Cyprinidae): effect of copper and cadmium exposure. Fish Physiology and Biochemistry, 38 (3), 745–756. doi: DOI:

Nadeau, D., Corneau, S., Plante, I., Morrow, G., Tanguay, R. M. (2001). Evaluation for Hsp70 as a biomarker of effect of pollutants on the earthworm Lumbricus terrestris. Cell stress & chaperones, 6 (2), 153–163. doi:<0153:efhaab>;2 DOI:<0153:EFHAAB>2.0.CO;2

Pearl, L. H., Prodromou, C. (2006). Structure and Mechanism of the Hsp90 Molecular Chaperone Machinery. Annual Review of Biochemistry, 75 (1), 271–294. doi: DOI:

Chang, Y.-W., Sun, Y.-J., Wang, C., Hsiao, C.-D. (2008). Crystal Structures of the 70-kDa Heat Shock Proteins in Domain Disjoining Conformation. Journal of Biological Chemistry, 283 (22), 15502–15511. doi: DOI:

Avdonin, P. P., Markitantova, Y. V., Poplinskaya, V. A., Grigoryan, E. N. (2013). Determination of mRNA-transcripts and heat shock proteins HSP70 and HSP90 in the retina of the adult Spanish Ribbed Newt Pleurodeles waltl. Biology Bulletin, 40 (4), 343–350. doi: DOI:

Tytell, M., Greenberg, S. G., Lasek, R. J. (1986). Heat shock-like protein is transferred from glia to axon. Brain Research, 363 (1), 161–164. doi: DOI:

Nita, M., Grzybowski, A. (2016). The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults. Oxidative Medicine and Cellular Longevity, 2016, 1–23. doi: DOI:

Maresca, A., la Morgia, C., Caporali, L., Valentino, M. L., Carelli, V. (2013). The optic nerve: A “mito-window” on mitochondrial neurodegeneration. Molecular and Cellular Neuroscience, 55, 62–76. doi: DOI:

Xiao, F., Li, Y., Dai, L., Deng, Y., Zou, Y., Li, P. (2012). Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes. International Journal of Molecular Medicine, 30 (3), 629–635. doi: DOI:

Mary Momo, C., Ferdinand, N., Omer Bebe, N., Alexane Marquise, M., Augustave, K., Bertin Narcisse, V. et. al. (2019). Oxidative Effects of Potassium Dichromate on Biochemical, Hematological Characteristics, and Hormonal Levels in Rabbit Doe (Oryctolagus cuniculus). Veterinary Sciences, 6 (1), 30. doi: DOI:

Bucio, L., Garcı́a, C., Souza, V., Hernández, E., González, C., Betancourt, M., Gutiérrez-Ruiz, M. C. (1999). Uptake, cellular distribution and DNA damage produced by mercuric chloride in a human fetal hepatic cell line. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 423 (1-2), 65–72. doi: DOI:

Castellino, N., Aloj, S. (1969). Intracellular distribution of lead in the liver and kidney of the rat. Occupational and Environmental Medicine, 26 (2), 139–143. doi: DOI:

Bolaños, J. P., Almeida, A., Fernández, E., Medina, J. M., Land, J. M., Clark, J. B., Heales, S. J. R. (1997). Potential mechanisms for nitric oxide-mediated impairment of brain mitochondrial energy metabolism. Biochemical Society Transactions, 25 (3), 944–949. doi: DOI:

Pandey, P., Saleh, A., Nakazawa, A., Kumar, S., Srinivasula, S. M., Kumar, V., Weichselbaum, R., Nalin, C., Alnemri, E. S., Kufe, D., Kharbanda, S. (2000). Negative regulation of cytochrome c-mediated oligomerization of Apaf-1 and activation of procaspase-9 by heat shock protein 90. The EMBO journal, 19 (16), 4310–4322. doi: DOI:

Gurbuxani, S., Schmitt, E., Cande, C., Parcellier, A., Hammann, A., Daugas, E. et. al. (2003). Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor. Oncogene, 22 (43), 6669–6678. doi: DOI:

Cavalcante, G. C., Schaan, A. P., Cabral, G. F., Santana-da-Silva, M. N., Pinto, P., Vidal, A. F., Ribeiro-dos-Santos, Â. (2019). A Cell’s Fate: An Overview of the Molecular Biology and Genetics of Apoptosis. International Journal of Molecular Sciences, 20 (17), 4133. doi: DOI:

Zou, H., Henzel, W. J., Liu, X., Lutschg, A., Wang, X. (1997). Apaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3. Cell, 90 (3), 405–413. doi: DOI:

Jedlicka, P., Mortin, M. A., Wu, C. (1997). Multiple functions of Drosophilaheat shock transcription factorin vivo. The EMBO Journal, 16 (9), 2452–2462. doi: DOI:

Ali, A., Bharadwaj, S., O’Carroll, R., Ovsenek, N. (1998). HSP90 Interacts with and Regulates the Activity of Heat Shock Factor 1 in Xenopus Oocytes. Molecular and Cellular Biology, 18 (9), 4949–4960. doi: DOI:

Dou, F., Chang, X., Ma, D. (2007). Hsp90 Maintains the Stability and Function of the Tau Phosphorylating Kinase GSK3β. International Journal of Molecular Sciences, 8 (1), 51–60. doi: DOI:

Zou, J., Guo, Y., Guettouche, T., Smith, D. F., Voellmy, R. (1998). Repression of Heat Shock Transcription Factor HSF1 Activation by HSP90 (HSP90 Complex) that Forms a Stress-Sensitive Complex with HSF1. Cell, 94 (4), 471–480. doi: DOI:

Abravaya, K., Myers, M. P., Murphy, S. P., Morimoto, R. I. (1992). The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression. Genes & Development, 6 (7), 1153–1164. doi: DOI:

Schoof, N., von Bonin, F., Trümper, L., Kube, D. (2009). HSP90 is essential for Jak-STAT signaling in classical Hodgkin lymphoma cells. Cell Communication and Signaling, 7 (1). doi: DOI:

Padmini, E., Usha Rani, M. (2011). Heat-shock protein 90 alpha (HSP90α) modulates signaling pathways towards tolerance of oxidative stress and enhanced survival of hepatocytes of Mugil cephalus. Cell Stress and Chaperones, 16 (4), 411–425. doi: DOI:

Bernstein, S. L., Russell, P., Wong, P., Fishelevich, R., Smith, L. E. (2001). Heat shock protein 90 in retinal ganglion cells: association with axonally transported proteins. Visual Neuroscience, 18 (3), 429–436. doi: DOI:

Ravagnan, L., Gurbuxani, S., Susin, S. A., Maisse, C., Daugas, E., Zamzami, N. et. al. (2001). Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nature Cell Biology, 3 (9), 839–843. doi: DOI:

Lorenzo, H. K., Susin, S. A., Penninger, J., Kroemer, G. (1999). Apoptosis inducing factor (AIF): a phylogenetically old, caspase-independent effector of cell death. Cell Death & Differentiation, 6 (6), 516–524. doi: DOI:

Kondrikov, D., Fulton, D., Dong, Z., Su, Y. (2015). Heat Shock Protein 70 Prevents Hyperoxia-Induced Disruption of Lung Endothelial Barrier via Caspase-Dependent and AIF-Dependent Pathways. PLOS ONE, 10 (6), e0129343. doi: DOI:

Shivers, R. R., Pollock, M., Bowman, P. D., Atkinson, B. G. (1988). The effect of heat shock on primary cultures of brain capillary endothelium: inhibition of assembly of zonulae occludentes and the synthesis of heat-shock proteins. European Journal of Cell Biology, 46 (1), 181–195.

Pournaras, C. J., Rungger-Brändle, E., Riva, C. E., Hardarson, S. H., Stefansson, E. (2008). Regulation of retinal blood flow in health and disease. Progress in Retinal and Eye Research, 27 (3), 284–330. doi: DOI:

Doll, D. N., Hu, H., Sun, J., Lewis, S. E., Simpkins, J. W., Ren, X. (2015). Mitochondrial Crisis in Cerebrovascular Endothelial Cells Opens the Blood–Brain Barrier. Stroke, 46 (6), 1681–1689. doi: DOI:

Connolly, N. M. C., Theurey, P., Adam-Vizi, V., Bazan, N. G., Bernardi, P., Bolaños, J. P. et. al. (2017). Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases. Cell Death & Differentiation, 25 (3), 542–572. doi: DOI:

Golpich, M., Amini, E., Mohamed, Z., Azman Ali, R., Mohamed Ibrahim, N., Ahmadiani, A. (2016). Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment. CNS Neuroscience & Therapeutics, 23 (1), 5–22. doi: DOI:

👁 17
⬇ 4
How to Cite
Kuzenko, O., Demin, Y., & Kuzenko, Y. (2020). RESEARCH OF REPARATIVE MECHANISMS IN THE OPTIC NERVE IN TOXIC NEUROPATHY CAUSED BY Cr (VI). ScienceRise, (6), 31-39.
Innovative technologies in healthcare