Mercury-Induced Oxidative Stress and Neuropathologic Changes in the Prefrontal Cortex of Wistar Rats

Authors

DOI:

https://doi.org/10.47081/njn2024.15.4/001

Keywords:

Mercury, Neurodegeneration, Neuroinflammation, Oxidative stress, Pollution

Abstract

Access to clean water is necessary for human, animal, and environmental health. Anthropogenic human activities such as mining, agriculture, and continuous pollution from industrial waste, as well as population growth, continue to compromise the quality of water. The neurodegenerative impact of mercury with a similar concentration as obtained from waterways on the prefrontal cortex of Wistar rats was studied. Twenty adult rats were randomised into two groups: a control group and a 0.001 mg/L mercury (II) thiocyanate (Hg(SCN)2) group, ad libitum for 65 days, after which the animals were euthanised via cervical dislocation. Blood and tissue samples were obtained for analyses of oxidative stress biomarkers: superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), hydrogen peroxide (H2O2), histological, and glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS) immunohistochemical evaluation. Statistical data were analysed using a t-test, set at p < 0.05. When comparing the mercury-treated groups to the control, a significant difference was observed in the SOD, GPx, MDA, and H2O2 values, with cellular alterations evident in the mercury-treated rats. Additionally, mercury treatment resulted in the distortion of the cortical histoarchitecture with intense immunoreactivity of GFAP and iNOS suggesting neuroinflammation. This study highlighted that mercury exposure induced oxidative stress and led to distortion in the histoarchitecture of the prefrontal cortex of adult Wistar rats.

Downloads

Download data is not yet available.

References

Adekomi, D.A., Adewole, O.S., Adekilekun, T.A. and Daniel, A.T. (2017) Lead induces inflammation and neurodegenerative changes in the rat medial prefrontal cortex. Anatomy. 11(2):79-86.

Adeniyi, T.D., Achukwu, P.U. and Abubakar, A.A. (2017). Frequency of electronics waste generated heavy metals in urban waterways. Int J Hum Cap Urban Manag. 2(2): 89-100.

Adeniyi, T.D., Achukwu, P.U., Abubakar, A.A. and Adekomi A.D. (2019) Heavy metals obtained from waterways induced neurodegeneration in the prefrontal cortex of Wistar rats. Eur J Anat. 23(1):65-76.

Adeniyi, T.D., Moronkeji, A. and Ekundina V.O. (2023) Histological evaluation of the liver, kidney, and tests of adult male Wistar rats exposed to heavy metals-contaminated waterways. Med Lab J. 17(5):4-8.

Adewole O.S. and Ayoka A.O. (2009) Beneficial role of Quercetin on developmental brain of rats against oxidative stress-induced by Lead poisoning. Pharmacologyonline. 2: 1171-1184.

Augustine, I.O., Gertrude, O.N., Martin, E., Obinna, U., Uchenna, E.K., Ogugua, E.A., et al. (2021) Cerebellar and hippocampal changes induced by lead in Wistar rats: The role of Ocimium gratissimium leaves extract. J BioMed. Sci. 10(3):56.

Azimi, A., Azari, A., Rezakazemi, M. and Ansarpour M. (2017) Removal of heavy metals from industrial wastewaters: A review. ChemBioEng Reviews. 4(1):37–59.

Bancroft, J.D. and Gamble, H. (2008) Theory, and Practice of Histological Technique, 6th edition, Philadelphia, PA: Churchill Livingstone/Elsevier. Pp 725.

Bharti, R. and Sharma, R. (2022) Effect of heavy metals: An overview. Materials Today: Proceedings, 51: 880-885.

Bopitiya, D., Christensen, D., Martin, M., Zhang, J. and Bennett, L.E. (2021) Production of hydrogen peroxide in formulated beverages is associated with the presence of ascorbic acid combined with selected redox-active functional ingredients. Food Chem. 338:127947.

Boujbiha, M.A., Hamden, K., Guermazi, F., Bouslama, A., Omezzine, A., Kammoun, A., et al. (2009) Testicular toxicity in mercuric chloride treated rats: association with oxidative stress. Reprod Toxicol. 28(1):81-89.

Bridges, C.C. and Zalups R.K. (2010) Transport of inorganic mercury and methylmercury in target tissues and organs. J Toxicol Environ Health Part B. 13(5):385–410.

Brown, G.C. (2010) Nitric oxide, and neuronal death. Nitric Oxide. 23: 153-165.

Carolin, C.F., Kumar P.S., Saravanan, A., Joshiba, G.J. and Naushad, M. (2017) Efficient techniques for the removal of toxic heavy metals from aquatic environment: A review. JECE. 5: 2782–2799.

Deger, O., Yigit, E., Korkmaz, K, Aygun, P., Asghari, A., Cakiroglu K.A. and Demir, S. (2023) Protective effect of bee products against oxidative damage in erythrocytes. GUJHS. 12(1):167-174.

Dehkordi, M.M., Nodeh, Z.P., Dehkordi, K.S., Khorjestan, R.R. and Ghaffarzadeh, M. (2024) Soil, air, and water pollution from mining and industrial activities: sources of pollution, environmental impacts, and prevention and control methods. Results in Engineering, 102729.

Delcambre, G.H., Lui, J., Herrington, J.M., Vallario, K. and Long, M.T. (2016) Immunohistochemistry for the detection of neural and inflammatory cells in equine brain tissue. PeerJ. 4:e1601.

Demir, F., Uzun, F.G., Durak, D. and Kalender, Y. (2011) Subacute chlorpyrifos-induced oxidative stress in rat erythrocytes and the protective effects of catechin and quercetin. Pesticide Biochem Physiol. 99(1):77-81.

Drury, R.A. and Wellington, E.A. (1980) Carleton Histological Technique. 5th ed. Oxford University Press, New York. Pp. 190.

Fernandes Azevedo, B., Barros Furieri, L., Peçanha, F.M., Wiggers, G.A., Frizera Vassallo, P., Ronacher Simões, M., et al. (2012) Toxic effects of mercury on the cardiovascular and central nervous systems. J Biomed Biotechnol. 2012:949048.

Foyer, C.H. and Noctor, G. (2005) Redox homeostasis and antioxidant signalling: a metabolic interface between stress perception and physiological responses. Plant Cell. 17(7): 1866-1875.

Gallo, G. and Martino, G. (2009) Red blood cell glutathione peroxidase activity in female nulligravid and pregnant rats. Reprod Biol Endocrinol. 7:7.

Goel, H., Goyal, K., Pandey, A.K., Benjamin, M., Khan, F., Pandey, P., et al. (2023) Elucidations of molecular mechanism and mechanistic effects of environmental toxicants in neurological disorders. CNS Neurol Disord Drug Targets. 22(1):84-97.

Hazelhoff, M.H., Bulacio, R.P. and Torres A.M. (2021) Trimetazidine protects from mercury induced kidney injury. Pharmacol. 106(5-6):332-340.

Hoehn, T., Felderhoff-Mueser, U., Maschewski, K., Stadelmann, C., Sifringer, M., Bittigau, P., et al. (2003) Hyperoxia causes inducible nitric oxide synthase-mediated cellular damage to the immature rat brain. Paediatric Res. 54(2):179-184.

Huang, D., Huang, H., Li, M., Fan, J., Sun, W., Du, J., et al. (2022) A tumor‐specific platform of peroxynitrite triggering ferroptosis of cancer cells. Advanced Functional Materials. 32(52):2208105.

Ibrahim, N.M., Eweis, E.A., El-Beltagi, H.S. and Abdul-Mobdy, Y.E. (2012) Effect of lead acetate toxicity on experimental male albino rat. Asian Pac. Trop. Biomed. 2(1):41-46.

Ijomone, O.M., Okori, S.O., Ijomone, O.K. and Ebokaiwe, A.P. (2018) Sub-acute nickel exposure impairs behavior, alters neuronal microarchitecture, and induces oxidative stress in rats' brain. Drug Chem Toxicol. 41(4):377-384.

Jadhav, S.H., Sarkar, S.N., Patil, R.D. and Tripathi, H.C. (2007) Effects of subchronic exposure via drinking water to a mixture of eight water-contaminating metals: A Biochemical and Histopathological study in male rats. Archives Environ. Contam Toxicol. 53(4):667-677.

Kang, B., Wang, J., Guo, S. and Yang, L. (2024) Mercury-induced toxicity: Mechanisms, molecular pathways, and gene regulation. Sci Total Environ. 943:173577.

Kapoor, D. and Singh, M.P. (2021) Heavy metal contamination in water and its possible sources. In: Kumar, V., Sharma, A. and Cerdà, A. (eds.), Heavy Metals in the Environment Impact, Assessment, and Remediation, Elsevier. Pp. 179-189.

Liu, W., Tang, Y. and Feng, J. (2011) Cross talk between activation of microglia and astrocytes in pathological conditions in the central nervous system. Life Sci. 89(5-6): 141-146.

Lyck, L., Dalmau, I., Chemnitz, J., Finsen, B. and Schroder H. D. (2008) Immunohistochemical markers for quantitative studies of neurons and glia in human neocortex. J Histochem Cytochem. 56(3):201-221.

Mahboob, M., Shireen, K.F., Atkinson, A. and Khan A.T. (2001) Lipid peroxidation and antioxidant enzyme activity in different organs of mice exposed to low level of mercury. J Environ Sci Health Part B. 36(5):687–697.

Mikulková, K., Illek, J. and Kadek, R. (2020) Glutathione redox state, glutathione peroxidase activity and selenium concentration in periparturient dairy cows, and their relation with negative energy balance. J Anim Feed Sci. 29(1):19-26.

Mistral, H.P. and Fridovich, J. (1972) The role of superoxide anion in the antioxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 247: 3170-3175.

Moronkeji, A. and Akinbo, F.O. (2024) Genotoxic Response and Histological alterations in rat lungs exposed to gasoline generator exhaust. Sultan Qaboos Univ J Sci 29(1):15–27.

National Academy Science (2011) Guide for the Care and Use of Laboratory Animals. Institute for Laboratory Animal Research. 8th ed. Washington, DC: National Academies Press. Pp. 60.

Novo, J.P., Martins, B., Raposo, R.S., Pereira, F.C., Oriá, R.B., Malva, J.O., et al. (2021). Cellular and molecular mechanisms mediating methylmercury neurotoxicity and neuroinflammation. Int J Mol Sci. 22(6):3101.

Olatunji, S.Y., Adewole, O.S., Ayannuga, O.A., Taiye, A.S., Adekomi, A.D., et al. (2015) Microanatomy and histomorphometry analysis of the effects of Moringa oleifera leaf extract on lead-induced kidney damage in adult Wistar rats. Int J Biol Chem Sci. 9(3):1599-1614.

Oliveira, A.C., Dionizio, A., Teixeira, F.B., Bittencourt, L.O., Lopes, M.G., Varela, L.P., et al. (2020) Hippocampal impairment triggered by long-term lead exposure from adolescence to adulthood in rats: insights from molecular to functional levels. Int J Mol Sci. 21(8):6937.

Owolabi, J., Williams, F. and Fabiyi, O. (2014) Evaluation of moringa’s effects against lead-induced disruption of the hippocampus in animal models. World J Life Sci Med Res. 3(2):39-45.

Pacher, P., Beckman, J.S. and Liaudet L. (2007) Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 87(1):315-424.

Paglia D.E. and Valentine W.N. (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 70:158-169.

Saha, R.N. and Pahan, K. (2006) Regulation of inducible nitric oxide synthase gene in glial cells. Antioxid Redox Signal. 8(5-6):929-947.

Said, E.S., Ahmed, R.M., Mohammed, R.A., Morsi, E.M., Elmahdi, M.H., Elsayed, H.S., et al. (2021) Ameliorating effect of melatonin on mercuric chloride-induced neurotoxicity. Heliyon. 7:e07485.

Shalan, M.G. (2022) Amelioration of mercuric chloride-induced physiologic and histopathologic alterations in rats using vitamin E and zinc chloride supplement. Heliyon. 8: e12036.

Sonone, S.S., Jadhav, S., Sankhla, M.S. and Kumar, R. (2020) Water contamination by heavy metals and their toxic effect on aquaculture and human health through food Chain. Lett Appl NanoBioScience, 10(2):2148-2166.

Stocks, J. and Dormandy, T.L. (1971) The autoxidation 0f human red cell lipid induced by hydrogen peroxide. Br J Haematol. 20(1):95-111.

Sudjarwo, S.A., Sudjarwo, G.W. and Koerniasari A. (2017) Protective effect of curcumin on lead acetate-induced testicular toxicity in Wistar rats. Res Pharmaceutical Sci 12(5):381-390.

Svendsen, P. and Hau, J. (1994) Selection, and handling of animals in biomedical research. Handbook of Laboratory Animal Science, volume 1, CRC Press. Pp. 120.

Takahashi, T. and Shimohata, T. (2019) Vascular Dysfunction Induced by Mercury Exposure. Int J Mol Sci. 20:2435

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

Tchounwou, P.B., Yedjou, C.G., Patlolla, A.K. and Sutton, D.J. (2012) Heavy metal toxicity and the environment. In: Luch, A. (ed.) Molecular, Clinical and Environmental Toxicology. Experientia Supplementum, Springer, Basel. 101. Pp 133-164

Uzun, F.G. and Kalender, Y. (2013) Chloropyrifos-induced hepatotoxicity and hematological changes in rats: The role of quercetin and catechin. Food Chem Toxicol. 55:549-556.

Uzunhisarcikli, M., Aslanturk, A., Kalender, S., Apaydin, F.G. and Bas, H. (2016) Mercuric chloride induced hepatotoxic and hematologic changes in rats: the protective effects of sodium selenite and vitamin E. Toxicol Industrial Health. 32(9):1651–1662.

Vardhan, K.H., Kumar, P.S. and Panda, R.C. (2019) A review on heavy metal pollution, toxicity, and remedial measures: J Mol Liq. 290:111197.

Villarín, M.C. and Merel S. (2020) Paradigm shifts and current challenges and in wastewater management. J Hazard Mater. 390: 122139.

Wolff, S.P. (1994). Ferrous ion oxidation in the presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Meth Enzymol. 233:182-189.

Wu, Y.S., Osman, A.I., Hosny, M., Elgarahy, A.M., Eltaweil, A.S., Rooney, D.W., et al. (2024). The toxicity of mercury and its chemical compounds: molecular mechanisms and environmental and human health implications: a comprehensive review. ACS Omega. 9(5): 5100-5126.

Xia, D., Yu, X., Liao, S., Shao, Q., Mou, H. and Ma, W. (2010) Protective effect of Smilax glabra extract against lead-induced oxidative stress in rats. J Ethnopharmacol. 130:414-420.

Zafar, A., Javed, S., Akram, N. and Naqvi, S.A.R. (2024). Health Risks of Mercury. In Mercury Toxicity Mitigation: Sustainable Nexus Approach (pp. 67-92). Cham: Springer Nature Switzerland.

Downloads

Published

2025-06-26

Issue

Section

Original Articles

How to Cite

Mercury-Induced Oxidative Stress and Neuropathologic Changes in the Prefrontal Cortex of Wistar Rats. (2025). Nigerian Journal of Neuroscience, 15(4), 97-104. https://doi.org/10.47081/njn2024.15.4/001

Similar Articles

11-14 of 14

You may also start an advanced similarity search for this article.