The effects of methanolic extract of Syzygium guineense (Wild.) D.C. on lead-induced neurotoxicity on the prefrontal cortex of Wistar rats

Victor Oluwafemi Makanjuola; Sodiq Kolawole Lawal; Clement I Ugwu; Simioluwa Ahmed; Samuel Oluwaseun Olojede; Wilfred Njabulo Nunu; Babatunde Adebola Alabi; Okikioluwa Stephen Aladeyelu

doi:10.61298/rans.2026.4.2.301

Authors

Victor Oluwafemi Makanjuola
Department of Anatomy, Bingham University, Karu, Nasarawa State, Nigeria
Sodiq Kolawole Lawal
[email protected]

Department of Anatomy and Physiology, Faculty of Medicine and Health Sciences, Private Bag UB 002, Plot 4775, Notwane Road, University of Botswana, Gaborone, Botswana
Clement I Ugwu
Department of Anatomy, Bingham University, Karu, Nasarawa State, Nigeria
Simioluwa Ahmed
College of Nursing Sciences, Lagos State University Teaching Hospital, Idi-Araba, Lagos, Nigeria
Samuel Oluwaseun Olojede
Department of Human Biology, Faculty of Medicine and Health Sciences, Walter Sisulu University, Nelson Mandela Drive, 5100, Mthatha, South Africa
Wilfred Njabulo Nunu
Department of Environmental and Occupational Health, School of Public Health, Faculty of Medicine and Health Sciences, University of Botswana, Gaborone, Botswana
Babatunde Adebola Alabi
Department of Basic and Clinical Pharmacology, School of Medicine, Rabinisia University, Tegeta, Dar Es Salaam, Tanzania
Okikioluwa Stephen Aladeyelu
Discipline of Clinical Anatomy, School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Medical School Campus, Durban, South Africa

Keywords:

Syzygium guineense, Lead acetate, Vacuolation, Neurotoxicity, Wistar rats

Abstract

Antimicrobial and wound-healing activities of Syzygium guineense are well documented, but its use in lead-induced neurotoxicity remains less explored. This study examined the effects of S. guineense leaf (SGL) extract on lead-induced prefrontal cortex (PFC) damage in Wistar rats. Twenty-five rats (60--80 g) were assigned to five groups (n = 5): control; lead (5 mg/kg); and lead + SGL extract at 100, 250, or 400 mg/kg. Behavior was assessed, and the PFC was excised for hematoxylin and eosin (H&E) and Cresyl Fast Violet (CFV) staining and for measurement of malondialdehyde (MDA), glucose-6-phosphate dehydrogenase (G6PDH), and lactate dehydrogenase (LDH) after two weeks of treatment. PFC MDA was significantly higher (P < 0.05) in the lead-only group than in the SGL-treated groups and control, and G6PDH differed significantly (P < 0.05) between the lead-only and SGL-treated groups. The lead-only and 100 mg/kg SGL groups showed vacuolation and neuronal cells. Cognitive function, PFC histoarchitecture, and Nissl staining improved in the 250 and 400 mg/kg SGL groups. These findings suggest that higher doses of SGL extract can potentially ameliorate lead-induced PFC damage.

Dimensions

REFERENCES

[1] M. Balali-Mood, K. Naseri, Z. Tahergorabi, M. R. Khazdair & M. Sadeghi, ``Toxic mechanisms of five heavy metals: mercury, lead, chromium, cadmium, and arsenic'', Frontiers in Pharmacology 12 (2021) 643972. https://doi.org/10.3389/fphar.2021.643972.

[2] S. Kianoush, M. Balali-Mood, S. R. Mousavi, V. Moradi, M. Sadeghi, B. Dadpour, O. Rajabi & M. T. Shakeri, ``Comparison of therapeutic effects of garlic and D-penicillamine in patients with chronic occupational lead poisoning'', Basic & Clinical Pharmacology & Toxicology 110 (2012) 476. https://doi.org/10.1111/j.1742-7843.2011.00841.x.

[3] N. N. Dongre, A. N. Suryakar, A. J. Patil, J. G. Ambekar & D. B. Rathi, ``Biochemical effects of lead exposure on systolic & diastolic blood pressure, heme biosynthesis and hematological parameters in automobile workers of north Karnataka (India)'', Indian Journal of Clinical Biochemistry 26 (2011) 400. https://doi.org/10.1007/s12291-011-0159-6.

[4] K. Shin, G. Lim, Y. S. Hong, S. Kim, S. Hwang, J. Lee, S. Sin, A. Cho, Y. Kim, R. Gautam & J. Jo, ``Exposure to lead on expression levels of brain immunoglobulins, inflammatory cytokines, and brain-derived neurotropic factor in fetal and postnatal mice with autism-like characteristics'', Journal of Toxicology and Environmental Health, Part A 84 (2021) 891. https://doi.org/10.1080/15287394.2021.1945985.

[5] J. Wang, H. Zhu, Z. Yang & Z. Liu, ``Antioxidative effects of hesperetin against lead acetate-induced oxidative stress in rats'', Indian Journal of Pharmacology 45 (2013) 395. https://doi.org/10.4103/0253-7613.115015.

[6] J. Wei, K. Du, Q. Cai, L. Ma, Z. Jiao, J. Tan, Z. Xu, J. Li, W. Luo, J. Chen & J. Gao, ``Lead induces COX-2 expression in glial cells in a NFAT-dependent, AP-1/NF$kappa$B-independent manner'', Toxicology 325 (2014) 67. https://doi.org/10.1016/j.tox.2014.08.012.

[7] D. Ramírez Ortega, D. F. González Esquivel, T. Blanco Ayala, B. Pineda, S. Gómez Manzo, J. Marcial Quino, P. Carrillo Mora & V. Pérez de la Cruz, ``Cognitive impairment induced by lead exposure during lifespan: mechanisms of lead neurotoxicity'', Toxics 9 (2021) 23. https://doi.org/10.3390/toxics9020023.

[8] Y. Fang, L. Lu, Y. Liang, D. Peng, M. Aschner & Y. Jiang, ``Signal transduction associated with lead-induced neurological disorders: a review'', Food and Chemical Toxicology 150 (2021) 112063. https://doi.org/10.1016/j.fct.2021.112063.

[9] C. J. Brubaker, K. N. Dietrich, B. P. Lanphear & K. M. Cecil, ``The influence of age of lead exposure on adult gray matter volume'', Neurotoxicology 31 (2010) 259. https://doi.org/10.1016/j.neuro.2010.03.004.

[10] B. Baars & N. M. Gage, Fundamentals of Cognitive Neuroscience: A Beginner's Guide, Academic Press, 2013. https://doi.org/10.1016/C2011-0-04186-8.

[11] Y. Yang & A. Raine, ``Prefrontal structural and functional brain imaging findings in antisocial, violent, and psychopathic individuals: a meta-analysis'', Psychiatry Research: Neuroimaging 174 (2009) 81. https://doi.org/10.1016/j.pscychresns.2009.03.012.

[12] P. Tugume, E. K. Kakudidi, M. Buyinza, J. Namaalwa, M. Kamatenesi, P. Mucunguzi & J. Kalema, ``Ethnobotanical survey of medicinal plant species used by communities around Mabira Central Forest Reserve, Uganda'', Journal of Ethnobiology and Ethnomedicine 12 (2016) 5. https://doi.org/10.1186/s13002-015-0077-4.

[13] M. Ekor, ``The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety'', Frontiers in Pharmacology 4 (2014) 177. https://doi.org/10.3389/fphar.2013.00177.

[14] I. C. Ezenyi & J. O. Igoli, ``Antidiarrhoeal properties of Syzygium guineense leaf extract and identification of chemical constituents in its active column fractions'', Journal of Complementary and Integrative Medicine 16 (2019) 20160074. https://doi.org/10.1515/jcim-2016-0074.

[15] P. Ghildyal, T. E. Grønhaug, A. Rusten, M. Skogsrud, B. Rolstad, D. Diallo, T. E. Michaelsen, M. Inngjerdingen & B. S. Paulsen, ``Chemical composition and immunological activities of polysaccharides isolated from the Malian medicinal plant Syzygium guineense'', Journal of Pharmacognosy and Phytotherapy 2 (2010) 76. https://doi.org/10.5897/JPP.9000018.

[16] J. Omale, A. Ogohi & G. Ebiloma, ``Anti-venom studies on Olax viridis and Syzygium guineense extracts against Naja katiensis venom in rats'', Planta Medica 79 (2013) PE23. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0033-1352042.

[17] J.-P. Noudogbessi, P. Yédomonhan, D. C. Sohounhloué, J.-C. Chalchat & G. Figuérédo, ``Chemical composition of essential oil of Syzygium guineense (Willd.) DC. var. guineense (Myrtaceae) from Benin'', Records of Natural Products 2 (2008) 33. Available online: https://www.researchgate.net/publication/26529875_Chemical_composition_of_essential_oil_of_Syzygium_guineense_Willd_DC_var_guineense_Myrtaceae_from_Benin.

[18] M. M. Draid, M. O. Bushwereb & S. G. Ramadan, ``Lead acetate toxicity on glucose level and liver enzymes ameliorated by camel's milk in wistar albino rat'', International Journal of Basic & Clinical Pharmacology 5 (2016) 1125. https://doi.org/10.18203/2319-2003.ijbcp20161580.

[19] M. Typlt, M. Mirkowski, E. Azzopardi, L. Ruettiger, P. Ruth & S. Schmid, ``Mice with deficient BK channel function show impaired prepulse inhibition and spatial learning, but normal working and spatial reference memory'', PLoS ONE 8 (2013) e81270. https://doi.org/10.1371/journal.pone.0081270.

[20] J. Stocks & T. Dormandy, ``The autoxidation of human red cell lipids induced by hydrogen peroxide'', British Journal of Haematology 20 (1971) 95. https://doi.org/10.1111/j.1365-2141.1971.tb00790.x.

[21] S. Adem & M. Ciftci, ``Purification of rat kidney glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase enzymes using 2',5'-ADP Sepharose 4B affinity in a single chromatography step'', Protein Expression and Purification 81 (2012) 1. https://doi.org/10.1016/j.pep.2011.08.031.

[22] A. Shahriari, N. J. Dawson, R. A. Bell & K. B. Storey, ``Stable suppression of lactate dehydrogenase activity during anoxia in the foot muscle of Littorina littorea and the potential role of acetylation as a novel posttranslational regulatory mechanism'', Enzyme Research 2013 (2013) 461374. https://doi.org/10.1155/2013/461374.

[23] V. Balamurugan, S. Fatima & S. Velurajan, ``A guide to phytochemical analysis'', International Journal of Advance Research and Innovative Ideas in Education 5 (2019) 236. Available online: https://ijariie.com/manuscript/9408.

[24] R. N. S. Yadav & M. Agarwala, ``Phytochemical analysis of some medicinal plants'', Journal of Phytology 3 (2011) 10. Available online: https://updatepublishing.com/journal/index.php/jp/article/view/2737.

[25] K. Santhi & R. Sengottuvel, ``Qualitative and quantitative phytochemical analysis of Moringa concanensis Nimmo'', International Journal of Current Microbiology and Applied Sciences 5 (2016) 633. https://doi.org/10.20546/ijcmas.2016.501.064.

[26] Y. Deng, X. Lin, J. Zhou, M. Li, Z. Fu & D. Song, ``Concurrent serum lead levels and cognitive function in older adults'', Frontiers in Neuroscience 17 (2023) 1180782. https://doi.org/10.3389/fnins.2023.1180782.

[27] R. Agarwal & A. Rami, ``Redistribution of glucose-6-phosphate dehydrogenase in response to cerebral ischemia in rat brain'', Indian Journal of Clinical Biochemistry 18 (2003) 64. https://doi.org/10.1007/BF02867369.

[28] E. M. M. Abd-Ella, S. F. El-Sisy & H. El-Dash, ``Protective effects of alpha lipoic acid ($alpha$-LA) against lead neuro-toxicity in albino rats'', International Journal of Pharmaceutical Science Invention 5 (2016) 5. Available online: https://www.ijpsi.org/Papers/Vol5(2)/B050205013.pdf.

[29] O. Owoeye & S. K. Onwuka, ``Lead toxicity: effect of Launaea taraxacifolia on the histological and oxidative alterations in rat regio III Cornu ammonis and cerebellum'', Anatomy Journal of Africa 5 (2016) 783. https://www.semanticscholar.org/paper/Lead-Toxicity%3A-Effect-of-Launaea-taraxacifolia-on-Owoeye-Onwuka/90b523d11c896870606017113b24b887e6528e9e.

[30] D. Praticò, C. M. Clark, F. Liun, J. Rokach, V. Y.-M. Lee & J. Q. Trojanowski, ``Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease'', Archives of Neurology 59 (2002) 972. https://doi.org/10.1001/archneur.59.6.972.

[31] A. F. Feudjio, R. Koularambaye, F. M. Jenny, A. Choupo, P. A. Z. Emini, D. L. M. Tsague, F. T. Nzufo & C. A. Pieme, ``Safety assessment of the aqueous bark extract of Syzygium guineense (Myrtaceae): acute and sub-chronic toxicity studies in rats'', Pharmacological Research--Natural Products 11 (2026) 100606. https://doi.org/10.1016/j.prenap.2026.100606.

[32] A. Ashraf, A. Liaquat, S. Shabbir, S. A. Bokhari, Z. Tariq, Z. Furrukh, A. A. Raja & M. J. Khan, ``High level of lactate dehydrogenase and ischaemia--reperfusion injury regulate the multiple organ dysfunction in patients with COVID-19'', Postgraduate Medical Journal 99 (2023) 576. https://doi.org/10.1136/postgradmedj-2022-141573.

[33] Z. Bauchi, D. Kizito, A. Alhassan, S. Akpulu & J. Timbuak, ``Effect of aqueous seed extract of Nigella sativa on lead-induced cerebral cortex toxicity in Long Evans rats'', Bayero Journal of Pure and Applied Sciences 9 (2016) 48. https://doi.org/10.4314/bajopas.v9i1.8.

[34] T. A. Etibor, M. I. Ajibola, M. O. Buhari, A. A. Safiriyu, O. B. Akinola & E. A. Caxton-Martins, ``Datura metel administration distorts medial prefrontal cortex histology of Wistar rats'', World Journal of Neuroscience 5 (2015) 282. https://doi.org/10.4236/wjns.2015.54026.

[35] I. Gersh & D. Bodian, ``Some chemical mechanisms in chromatolysis'', Journal of Cellular and Comparative Physiology 21 (1943) 253. https://doi.org/10.1002/jcp.1030210305.