Reprofiling Of Ormeloxifene For Its Neuroprotective Activity Against Monosodium Glutamate And Aluminium Chloride Induced Neurotoxicity In Rats
Abstract
Background: Monosodium glutamate (MSG) and Aluminium chloride (AlCl3) are known to induce neurotoxicity, which can lead to cognitive deficits and neuronal damage. Due to the neuroprotective role of Ormeloxifene, it is evaluated against chemically (MSG) and (AlCl3) induced neurotoxicity in rats.
Materials & Methods: Male Wistar albino rats were divided into two neurotoxicity models with 60 rats in each model. Rats were administered ormeloxifene at different doses (2.5, 5.1 and 10.2 mg/kg p.o) for 14 days AlCl3 model and 21 days MSG model. Neurobehavioral parameters such as locomotor activity, muscle coordination and spatial memory were carried out. Antioxidant enzyme estimated such as lipid peroxidation (LPO) and glutathione (GSH) along with acetylcholinesterase (AChE). Histopathology studies were also carried out.
Results: Ormeloxifene co-treatment significantly reduced cognitive deficits, improved locomotor activity, muscle coordination, reference memory and spatial memory. It also reduced acetylcholinesterase (AchE) and lipid peroxidation (LPO) activity, while increasing glutathione (GSH) concentration. Histopathology reports showed reduced neuronal damage.
Conclusion: Ormeloxifene demonstrated neuroprotective effects against MSG and AlCl3-induced neurotoxicity in rats, potentially due to its ability to activate kinases and inhibit nuclear factor (NF)-kB induced transcription. These findings suggest Ormeloxifene as a potential therapeutic agent for neuroprotection
Downloads
References
Kovacs GG. Concepts and classification of neurodegenerative diseases. In Handbook of clinical neurology 2018 Jan 1 (Vol. 145, pp. 301-307). Elsevier.
Chi H, Chang HY, Sang TK. Neuronal cell death mechanisms in major neurodegenerative diseases. International journal of molecular sciences. 2018 Oct 9;19(10):3082.
Logroscino G, Urso D, Savica R. Descriptive epidemiology of neurodegenerative diseases: what are the critical questions?. Neuroepidemiology. 2022 Jun 21;56(5):309-18.
Chen WW, Zhang XI, Huang WJ. Role of neuroinflammation in neurodegenerative diseases. Molecular medicine reports. 2016 Apr 1;13(4):3391-6.
Umukoro S, Oluwole GO, Olamijowon HE, Omogbiya AI, Eduviere AT. Effect of monosodium glutamate on behavioral phenotypes, biomarkers of oxidative stress in brain tissues and liver enzymes in mice. World Journal of neuroscience. 2015 Sep 18;5(5):339-49.
Ahanger IA, Bashir S, Parray ZA, Alajmi MF, Hussain A, Ahmad F, Hassan MI, Islam A, Sharma A. Rationalizing the role of monosodium glutamate in the protein aggregation through biophysical approaches: Potential impact on neurodegeneration. Frontiers in neuroscience. 2021 Mar 4;15:636454.
Maya S, Prakash T, Madhu KD, Goli D. Multifaceted effects of aluminium in neurodegenerative diseases: A review. Biomedicine & Pharmacotherapy. 2016 Oct 1;83:746-54.
Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, Doig A, Guilliams T, Latimer J, McNamee C, Norris A. Drug repurposing: progress, challenges and recommendations. Nature reviews Drug discovery. 2019 Jan;18(1):41-58.
Arevalo MA, Santos-Galindo M, Lagunas N, Azcoitia I, Garcia-Segura LM. Selective estrogen receptor modulators as brain therapeutic agents.
Kumar Gara R, Sundram V, C Chauhan S, Jaggi M. Anti-cancer potential of a novel SERM ormeloxifene. Current medicinal chemistry. 2013 Nov 1;20(33):4177-84.
Reddy D, shindey S, Kilaru NB, Pingili R. Evaluation of skeletal muscle relaxant activity of quercetin and chrysin in Albino rats using rota-rod apparatus and actophotometer. Iranian Journal of Pharmacology and Therapeutics. 2017 Jun 10;15(1):1-4.
Deacon RM. Measuring motor coordination in mice. JoVE (Journal of Visualized Experiments). 2013 May 29(75):e2609.
Sun XY, Li LJ, Dong QX, Zhu J, Huang YR, Hou SJ, Yu XL, Liu RT. Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer’s disease. Journal of neuroinflammation. 2021 Dec;18(1):1-4.
Morris RG, Garrud P, Rawlins JA, O'Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature. 1982 Jun 24;297(5868):681-3.
Nunez J. Morris water maze experiment. JoVE (Journal of Visualized Experiments). 2008 Sep 24(19):e897.
Ranpariya VL, Parmar SK, Sheth NR, Chandrashekhar VM. Neuroprotective activity of Matricaria recutita against fluoride-induced stress in rats. Pharmaceutical biology. 2011 Jul 1;49(7):696-701.
Ellman GL, Courtney KD, Andres Jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical pharmacology. 1961 Jul 1;7(2):88-95.
Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry. 1968 Jan 1;25:192-205.
Jagota SK, Dani HM. A new colorimetric technique for the estimation of vitamin C using Folin phenol reagent. Analytical biochemistry. 1982 Nov 15;127(1):178- 82.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry. 1979 Jun 1;95(2):351-8.
Klaassen C D. Casarett and Doull’s Toxicology: The basic science of poisons. 7thed. McGraw-Hill medical publishing Division; 2010.
S. Bolognin, L. Messori, D. Drago, C. Gabbiani, L. Cendron, P. Zatta, Aluminum, copper, iron and zinc differentially alter amyloid-Abeta(1-42) aggregation and toxicity, Int. J. Biochem. Cell Biol. 43 (6) (2011) 877–885.
J.T. Arokiasamy, R.W.R. Tharsius, J. Udaiyappan, M. Thamilarasan, Neuroprotective effect of hesperidin on aluminium chloride induced Alzheimer’s disease in Wistar Rats, Neurochem. Res. 40 (2015) 767–776.
Liaquat L, Sadir S, Batool Z, Tabassum S, Shahzad S, Afzal A, Haider S. Acute aluminum chloride toxicity revisited: Study on DNA damage and histopathological, biochemical and neurochemical alterations in rat brain. Life sciences. 2019 Jan 15;217:202-11.
Ali AA, Ahmed HI, Khaleel SA, Abu-Elfotuh K. Vinpocetine mitigates aluminum-induced cognitive impairment in socially isolated rats. Physiology & behavior. 2019 Sep 1;208:112571.
I. Ghazala, I. Anila, M. Aamra, M.F. Syeda, A. Touqeer, Memory enhancing effect of black pepper in the AlCl3 induced neurotoxicity mouse model is mediated through its active component chavicine, Curr. Pharm. Biotechnol. 17 (2016), 000-000.
K.D. Parekh, R.P. Dash, A.N. Pandya, K.K. Vasu, M. Nivsarkar, Implication of novel bis-imidazopyridines for management of Alzheimer’s disease and establishment of its role on protein phosphatase 2A activity in brain, J. Pharm. Pharmacol. 65 (2013) 1785–1795.
H.H. Ahmed, S.F. Estefan, E.M. Mohamd, A.H. Farrag, R.S. Salah, Does melatonin ameliorate neurological changes associated with Alzheimer’s disease in ovariectomized rat model? Indian J. Clin. Biochem. 23 (2013), 381-19.
H.Q. Li, S.P. Ip, G.Q. Zheng, Y.F. Xian, Z.X. Lin, Isorhynchophylline alleviates learning and memory impairments induced by aluminum chloride in mice, Chin. Med. 23 (2018) 13–29.
A. Justin, T.R. William, U. Janakiraman, T. Manivasagam, Neuroprotective effect of hesperidin on aluminium chloride induced Alzheimer’s disease in wistarrats,mNeurochem. Res. 40 (2015) 767–776.
P.K. Mukherjee, V. Kumar, N.S. Kumar, M. Heinrich, The Ayurvedic medicine Clitoriaternatea—from traditional use to scientific assessment, J. Ethnopharmacol. 20 (3) (2008) 291–301.
Singh, K.; Pushpa, A. Alteration in some antioxidant enzymes in cardiac tissue upon monosodium glutamate [MSG] administration to adult male mice. Indian J. Clin. Biochem. 2005, 20, 43–46.
Cabrera, G.G.; Ureña-Guerrero, M.E.; Rivera-Cervantes, M.C.; Feria-Velasco, A.I.; Beas-Zarate, C. Excitotoxicity triggered by neonatal monosodium glutamate treatment and blood–brain barrier function. Arch. Med Res. 2014, 45, 653–659.
Hassaan, P.S.; Dief, A.E.; Zeitoun, T.M.; Baraka, A.M.; Deacon, R.M.J.; Elshorbagy, A. Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life. PLoS ONE 2019, 14, e0220720.
López-Pérez, S.J.; Ureña-Guerrero, M.E.; Morales-Villagrán, A. Morales-Villagrán, Monosodium glutamate neonatal treatment as a seizure and excitotoxic model. Brain Res. 2010, 1317, 246–256.
Shivasharan, B.D.; Nagakannan, P.; Thippeswamy, B.S.; Veerapur, V.P. Protective effect of Calendula officinalis L. flowers against monosodium glutamate induced oxidative stress and excitotoxic brain damage in rats. Indian J. Clin. Biochem. 2013, 28, 292–298.
Sanabria, E.; Pereira, M.; Dolnikoff, M.; Andrade, I.; Ferreira, A.; Cavalheiro, E.A.; Fernandes, M.J.D.S. Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats. Brain Res. Bull. 2002, 59, 47–51.
Colín-González, A.L.; Ali, S.F.; Túnez, I.; Santamaría, A. On the antioxidant, neuroprotective and anti-inflammatory properties of S-allyl cysteine: An update. Neurochem. Int. 2015, 89, 83–91.
Lau, A.; Tymianski, M. Glutamate receptors, neurotoxicity and neurodegeneration. Pflüg. Arch.-Eur. J. Physiol. 2010, 460, 525–542..
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Suma G, Mallappa Shalavadi, Shubham Teli, Mounashree U, Rajashekhar N, Shivaraj Hiremath, Basavaraj H
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
