Neuroprotective Efficacy of Eugenol Against Lead Acetate and Monosodium Glutamate Induced Neurotoxicity by Modulating Brain-Derived Neurotrophic Factor (BDNF) Gene Expression in Wistar Rats

Download Article

DOI: 10.21522/TIJPH.2013.13.01.Art048

Authors : Karthik Ganesh Mohanraj, Vidya Ganapathy

Abstract:

The human nervous system is highly susceptible to various environmental toxins, which can lead to neurodegenerative conditions characterized by cognitive deficits, motor dysfunction, and even cell death. Among these toxins, lead (Pb) and Monosodium Glutamate (MSG) have been evaluated in this study for their neurotoxic effects. Lead exposure has been associated with detrimental effects on the central nervous system, similarly, MSG, a common food additive, has been reported to induce neurotoxicity through oxidative stress and excitotoxicity mechanisms. Eugenol, found in essential oils, have demonstrated promising antioxidant, anti-inflammatory and neuroprotective properties. Hence Eugenol was used as a therapeutic agent against lead acetate and MSG induced neurotoxicity by modulating Brain-derived Neurotrophic Factor. This in vivo study involved 48 Wistar albino rats, divided into eight groups consisting of Control, Lead acetate induction (100 mg/kg b.wt for 30 days), MSG induction (2 g/kg b.wt for 21 days) and subsequent treatment with Eugenol (250 mg/kg b.wt for 30 days) in comparison with positive control, memantine (20mg/kg b.wt for 15 days). Histopathological and BDNF gene expression were evaluated after the experimental period. Histopathological analysis confirmed that eugenol preserved neuronal integrity, reducing neuronal damage caused by lead acetate and MSG exposure by modulating free radical generation upon oxidative stress. Eugenol treatment in rats exposed to lead and MSG resulted in a significant upregulation of BDNF expression (p<0.01) compared to the untreated toxin-exposed groups. These outcomes suggest that Eugenol could be a possible therapeutic agent for protecting the neuronal tissues from Lead acetate and MSG-induced neurotoxicity.

References:

[1].   Flora, G., Gupta, D., & Tiwari, A., 2012, Toxicity of lead: A review with recent updates. Interdisciplinary Toxicology, 5(2), 47-58. https://doi.org/10.2478/v10102-012-0009-2

[2].   Ganesan, B., Budin, S. B., & Anuar, I., 2022, Monosodium glutamate-induced oxidative stress and cognitive impairments in rats: Neuroprotective effects of natural antioxidants. Food and Chemical Toxicology, 167, 113232. https://doi.org/10.1016%2FaCtox.2024.100148

[3].   Park, S. E., Sapkota, K., Choi, J. H., 2011, Eugenol protects neuronal cells from oxidative stress-induced apoptosis through TRPV1 activation. https://doi.org/10.3892%2Fetm.2020.9539

[4].   Meenakshi, S., Varghese, S. S., Mohanraj K. G., 2023, Bone Regenerative Potential of a Recombinant Parathormone Derivative in Experimentally Induced Critical-size Calvarial Defects in Wistar Albino Rats. World J Dent 14(5):452–461.

[5].   Solmaz Mohammad Inejad, 2017, “Pharmacological and toxicological properties of eugenol” Turk J Pharm Sci, https://doi.org/10.4274%2Ftjps.62207

[6].   Prakash Binu, 2018, “Protective Effects of Eugenol Against Hepatotoxicity Induced By Arsenic Trioxide: An Antileukemic Drug” IJMS vol 43, no 3.

[7].   Hanna, S. S., Gazwi, 2020, “Mitigation of lead neurotoxicity by the ethanolic extract of Laurus leaf in rats” Exotoxicol Environ Saf Apr 1:192:110297. doi: 10.1016/j.ecoenv.2020.110297.

[8].   Fasakin, O. W., A. O. Fajobi, and O. O. Oyedapo, 2017, "Neuroprotective potential of Aframomum melegueta extracts on brain of monosodium glutamate-treated wistar albino rats." Journal of Neuroscience and Behavioral Health 9.2 (2017): 16-27. DOI: 10.5897/JNBH2017.0145

[9].   Varsha Singh, 2013, “In vivo antioxidative and neuroprotective effect of 4-Allyl-2- methoxyphenol against chlorpyrifos-induced neurotoxicity in rat brain” Mol cell biochem, Mar;388(1-2):61-74. doi: 10.1007/s11010-013-1899-9. Epub 2013 Dec 1.

[10].  Rajagopal shanmuga Sundaram, 2013, “Neuroprotective potential of Ocimum sanctum (Linn) leaf extract in monosodium glutamate induced excitotoxicity” African Journal of Pharmacy and Pharmacology 7(27):1894-1906 DOI:10.5897/AJPP12.1445

[11].  Bancroft, J. D., and Gamble, M., 2002, “Theory and Practice of Histological Techniques,” Churchill Livingstone, London.

[12].  Sasi, M., Vignoli, B., Canossa, M., & Blum, R., 2017, Neurobiology of local and intercellular BDNF signaling. Pflügers Archiv-European Journal of Physiology, 469(5), 593-610. https://doi.org/10.1007/s00424-017-1964-4

[13].  Patapoutian, A., & Reichardt, L. F., 2001, Trk receptors: mediators of neurotrophin action. Current Opinion in Neurobiology, 11(3), 272-280. https://doi.org/10.1016/s0959-4388(00)00208-7

[14].  Mahmoud, S., Gharagozloo, M., Simard, C., Gris, D., 2019, Microglia and neuroinflammation: modulation by exercise. Journal of Neuroinflammation, 16, 138. https://doi.org/10.3389%2Ffnins.2023.1125428.

[15].  Pandiar, D., Ramani, P., Krishnan R. P., Y., Dinesh, Histopathological analysis of soft tissue changes in gingival biopsied specimen from patients with underlying corona virus disease associated mucormycosis (CAM), https://doi.org/10.4317/medoral.25050.

[16].  Souparnika.V., Karthik Ganesh Mohanraj, Vidya, S., Antioxidant activity of L-Theanine on Cadmium Induced oxidative stress mediated neurodegeneration-An invivo analysis, https://doi.org/10.47750/jptcp.2022.952.

[17].  Sanders, T., Liu, Y., Buchner, V., & Tchounwou, P. B., 2009, Neurotoxic effects and biomarkers of lead exposure: A review. Reviews on Environmental Health, 24(1), 15-45. https://doi.org/10.1515/reveh.2009.24.1.15.

[18].  Sanjay Varshan, M., Lavanya Prathap, Selvaraj Jayaraman, Preetha, S., 2022, Anti Proliferative Effect of Endogenous Dopamine Replica in Human Lung Cancer Cells (A549) Via Pi3k and Akt Signalling Molecules. https://doi.org/10.47750/pnr.2022.13.S03.215.

[19].  Lu, B., Nagappan, G., & Lu, Y., 2013, BDNF and synaptic plasticity, cognitive function, and dysfunction. Handbook of Experimental Pharmacology, 220, 223-250. https://doi.org/10.1007/978-3-642-45106-5_9.

[20].  Rattiner, L. M., Davis, M., French, C. T., & Ressler, K. J. 2004, Brain-derived neurotrophic factor and tyrosine kinase receptor B involvement in amygdala-dependent fear conditioning. Journal of Neuroscience, 24(20), 4796-4806. https://psycnet.apa.org/doi/10.1523/JNEUROSCI.5654-03.2004

[21].  Toscano, C. D., & Guilarte, T. R., 2005, Lead neurotoxicity: From exposure to molecular effects. Brain Research Reviews, 49(3), 529-554 https://doi.org/10.1016/j.brainresrev.2005.02.004.

[22].  Nagababu, E., Rifkind, J. M., Boindala, S., & Nakka, L., 2010, Assessment of antioxidant activity of eugenol in vitro and in vivo. Free Radical Biology and Medicine, 49(1), 144-153. https://doi.org/10.1007/978-1-60327-029-8_10.

[23].  Giridharan, V. V., Thandavarayan, R. A., Sato, S., Ko, K. M., Ma, M., & Suzuki, K., 2011, Eugenol attenuates neuroinflammatory responses and cognitive dysfunction in a transgenic mouse model of Alzheimer's disease. Journal of Biological Chemistry, 286(43), 37716-37727. http://dx.doi.org/10.3109/10715762.2011.571682

[24].  Lu, B., Nagappan, G., & Lu, Y., 2013, BDNF and synaptic plasticity, cognitive function, and dysfunction. Handbook of Experimental Pharmacology, 220, 223-250. https://doi.org/10.1007/978-3-642-45106-5_9

[25].  Saleh, D. O., Baraka, S. M., Jaleel, G. A. A., Hassan, A., Ahmed-Farid, O. A., 2024, Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling. Sci Rep. 2024 Jan 22;14(1):1910. doi: 10.1038/s41598-024-52259-1. PMID: 38253778; PMCID: PMC10803763.

[26].  Allen, S. J., Dawbarn, D., & Wilcock, G. K., 2011, BDNF levels in Alzheimer's disease: implications for neuroprotective strategies. Journal of Alzheimer’s Disease, 22(1), 43-56. https://doi.org/10.2174%2F157015911798376190

[27].  Marvanová, M., Menager, J., Bezard, E., & Bockaert, J., 2001, Reduced brain-derived neurotrophic factor expression in the frontal cortex in Alzheimer's disease. Neurobiology of Aging, 22(2), 267-272. https://doi.org/10.1016/s0169-328x(97)00125-3

[28].  Dwivedi, Y., Rizavi, H. S., Conley, R. R., Roberts, R. C., Tamminga, C. A., & Pandey, G. N., 2003, Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Archives of General Psychiatry, 60(8), 804-815. https://doi.org/10.1001/archpsyc.60.8.804

[29].  Martinez-Herrera, A., Pozos-Guillen, A., Ruiz-Rodriguez, S., Garrocho-Rangel, A., Vertiz-Hernandez, A., Escobar-Garcia, D. M., 2016, Effect of 4-allyl-1-hydroxy-2-methoxybenzene (eugenol) on inflammatory and apoptosis processes in dental pulp fibroblasts. Mediators of Inflammation, 2016 doi: 10.1155/2016/9371403.9371403

[30].  Harb, A. A., Bustanji, Y. K., Almasri, I. M., Abdalla, S. S., Eugenol, reduces LDL cholesterol and hepatic steatosis in hypercholesterolemic rats by modulating TRPV1 receptor. Scientific Reports. 2019;9(1):p. 14003. doi: 10.1038/s41598-019-50352-4.

[31].  Miranda, M., Morici, J. F., Zanoni, M. B., Bekinschtein, P., Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain. Front. Cell. Neurosci. 2019;13:1–25. doi: 10.3389/fncel.2019.00363

[32].  Mitre, M., Mariga, A., Chao, M. V., Neurotrophin Signalling: Novel Insights into Mechanisms and Pathophysiology. Clin. Sci. 2017;131:13–23. doi: 10.1042/CS20160044.

[33].  Nisar, M. F., Khadim, M, Rafiq, M., Chen J., Yang Y., Wan C. C., Pharmacological Properties and Health Benefits of Eugenol: A Comprehensive Review. Oxid Med Cell Longev. 2021 Aug 3;2021:2497354. doi: 10.1155/2021/2497354. PMID: 34394824; PMCID: PMC8357497.

[34].  Ebenezer Leonoline, J., Gunapriya, R., Ranganathan, K., Vijayaraghavan, R., Ganesh Karthik, M., 2021, Determine Cyp17a1 and Ki67 Expressions in Pcos Induced Rat Model Treated with Sepia pharaonis Ink Extract Proves Effective. Indian Journal of Animal Research. 55(10): 1206-1214. doi: 10.18805/IJAR.B-4204.