Neuroprotective effects of Huperzine-A in aluminum induced neurotoxicity in hippocampus of mice
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Aluminum, Hippocampus, Acetylcholinesterase, Huperzine A, Neuroprotection
Abstract
Exposure to aluminum has been correlated with the epidemiology of Alzheimer’s disease. Huperzine A (HupA), derived from the Chinese herb Huperzia serrata, is an inhibitor of acetylcholinesterase (AChE). However, its use in aluminum induced neurotoxicity has not been reported. The objective of the study was to examine the effect of HupA on aluminum-induced changes in AChE activity and hippocampal neurotoxicity. Aged female swiss albino mice were divided into five groups (n=10). Aluminum treated group (Al-S) received 30 mg/Kg of aluminum chloride (AlCl3) intraperitoneally (IP) for two weeks followed by IP normal saline. Three HupA treated groups received similar IP dosage of AlCl3 for two weeks followed by HupA 0.1 mg/Kg, HupA 0.2 mg/Kg and HupA 0.5 mg/kg. Control group received IP normal saline. At the end of week 4, AChE was estimated, and pyramidal neurons of hippocampus were counted. Al-S group showed an increase in mean brain AChE and Al-HupA 0.1 reduced it significantly (p<0.05). Reduction in mean neuronal density in Al-S group, was comparatively more in CA3 hippocampal area (p<0.001). Quantitative study found that 0.2mg/Kg of synthetic Huperzine A given intraperitoneally, was able to increase neuronal count significantly compared to 0.1mg/Kg and 0.5mg/Kg of Huperzine A.
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References
Crapper, D. R., Krishnan, S. S., Dalton, A. J. 1973. Brain aluminium distribution in Alzheimer’s disease and experimental neurofibrilarry degeneration. Science, 180(4085):511–513.
Exley, C. 2004. The pro-oxidant activity of aluminum. Free Radical Biology and Medicine, 36(3):380–387.
Flaten, T. P. 1990. Geographical associations between aluminium in drinking water and death rates with dementia (including Alzheimer’s disease), Parkinson’s disease and amyotrophic lateral sclerosis in Norway. Environmental Geochemistry and Health, 12(1-2):152–167.
Gulya, K., Rakonczay, Z., Kása, P. 1990. Cholinotoxic effects of aluminum in rat brain. Journal of Neurochemistry, 54(3):1020–1026.
Gutteridge, J. M., Quinlan, G. J., Clark, I., Halliwell, B. 1985. Aluminium salts accelerate peroxidation of membrane lipids stimulated by iron salts. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 835(3):441–447.
Hanin, I., Tang, X. C., Kindel, G. L., Kozikowski, A. P. 1993. Natural and Synthetic Huperzine A: Effect on Cholinergic Function in Vitro and in Vivo. Annals of the New York Academy of Sciences, 695(1):304–306.
Kobayashi, S., Hirota, N., Saito, K., Utsuyama, M. 1987. Aluminum accumulation in tangle-bearing neurons of Alzheimer’s disease with Balint’s syndrome in a long-term aluminum refiner. Acta Neuropathologica, 74(1):47–52.
Kong, S., Liochev, S., Fridovich, I. 1992. Aluminum(III) facilitates the oxidation of NADH by the superoxide anion. Free Radical Biology and Medicine, 13(1):79–81.
Krishnan, K., Mitra, N. K., Yee, L. S., Yang, H. M. 2012. A comparison of neurotoxicity in cerebellum produced by dermal application of chlorpyrifos in young and adult mice. Journal of Neural Transmission, 119(3):345–352.
Lazarov, O., Hollands, C. 2016. Hippocampal neurogenesis: Learning to remember. Progress in Neurobiology, 138-140:1–18.
Liang, Y.-Q., Tang, X.-C. 2006. Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats. Acta Pharmacologica Sinica, 27(9):1127–1136.
Maya, S., Prakash, T., Madhu, K. D., Goli, D. 2016. Multifaceted effects of aluminium in neurodegenerative diseases: A review. Biomedicine and Pharmacotherapy, 83:746–754.
McLachlan, D. R., Bergeron, C., Smith, J. E., Boomer, D., Rifat, S. L. 1996. Risk for neuropathologically confirmed Alzheimer’s disease and residual aluminum in municipal drinking water employing weighted residential histories. Neurology, 46(2):401–405.
Méndez-Álvarez, E., Soto-Otero, R., Hermida-Ameijeiras, A., López-Real, A. M., Labandeira-García, J. L. 2002. Effects of aluminum and zinc on the oxidative stress caused by 6-hydroxydopamine autoxidation: relevance for the pathogenesis of Parkinson’s disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1586(2):155–168.
Miu, A. C., Andreescu, C. E., Vasiu, R., Olteanu, A. I. 2003. A behavioral and histological study of the effects of long-term exposure of adult rats to aluminum. International Journal of Neuroscience, 113(9):1197–1211.
Mushtaq, G., Greig, N. H., Khan, J. A., Kamal, M. A. 2014. Status of acetylcholinesterase and butyrylcholinesterase in Alzheimer’s disease and type 2 diabetes mellitus. CNS and Neurological Disorders - Drug Targets, 13(8):1432–1439.
Rondeau, V., Commenges, D., Jacqmin-Gadda, H., Dartigues, J. F. 2000. Relation between aluminum concentrations in drinking water and Alzheimer’s disease: an 8-year follow-up study. American Journal of Epidemiology, 152(1):59–66.
Sánchez-Iglesias, S., Soto-Otero, R., Iglesias-González, J., Barciela-Alonso, M. C., Bermejo-Barrera, P., Méndez-Álvarez, E. 2007. Analysis of brain regional distribution of aluminium in rats via oral and intraperitoneal administration. Journal of Trace Elements in Medicine and Biology, 21(Supplement 1):31–34.
Senger, M. R., Seibt, K. J., Ghisleni, G. C., Dias, R. D., Bogo, M. R., Bonan, C. D. 2011. Aluminum exposure alters behavioral parameters and increases acetyl- cholinesterase activity in zebrafish (Danio rerio) brain. Cell Biology and Toxicology, 27(3):199–205.
Sethi, P., Jyoti, A., Singh, R., Hussain, E., Sharma, D. 2008. Aluminium-induced electrophysiological, biochemical and cognitive modifications in the hippocampus of aging rats. NeuroToxicology, 29(6):1069–1079.
Soni, M. G., White, S. M., Flamm, W. G., Burdock, G. A. 2001. Safety evaluation of dietary aluminium. Regulatory Toxicology and Pharmacology, 33(1):66–79.
Tang, X. C., Kindel, G. H., Kozikowski, A. P., Hanin, I. 1994. Comparison of the effects of natural and synthetic huperzine-A on rat brain cholinergic function in vitro and in vivo. Journal of Ethnopharmacology, 44(3):147–155.
Verstraeten, S. V., Oteiza, P. I. 2000. Effects of Al3+ and related metals on membrane phase state and hydration: correlation with lipid oxidation. Archives of Biochemistry and Biophysics, 375(2):340–346.
Wang, T., Tang, X. C. 1998. Reversal of scopolamine-induced deficits in radial maze performance by (-)- Huperzine A: comparison with E2020 and tacrine. European Journal of Pharmacology, 349(2-3):137–142.
Xu, S. S., Cai, Z. Y., Qu, Z. W., Yang, R. M., Cai, Y. L., Wang, G. Q., Su, X. Q., Zhong, X. S., Cheng, R. Y., Xu, W. A., Li, J. X., Feng, B. 1999. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo Yao Li Xue Bao, 20(6):486–490.
Yang, G., Wang, Y., Tian, J., Liu, J. P. 2013. Huperzine A for Alzheimer’s disease: a systematic review and meta-analysis of randomized clinical trials. PLoS ONE, 8(9):e74916.
Yellamma, K., Saraswathamma, S., Kumari, B. N. 2010. Cholinergic system under aluminium toxicity in rat brain. Toxicology International, 17(2):106–112.
Zaman, K., Zaman, W., Siddique, H. 1993. Hematological and enzymatic results of aluminum intoxication in rats. Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, 105(1):73–76.
Zangara, A. 2003. The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer’s disease. Pharmacology Biochemistry and Behavior, 75(3):675–686.
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