بررسی اثر الاژیک اسید بر اختلالات حرکتی و حافظه ناشی از 6- هیدروکسی دوپامین در موش صحرایی نر
محورهای موضوعی : فصلنامه زیست شناسی جانوریزینب عیدی پور 1 , مریم رفیعی راد 2
1 - گروه زیست شناسی، واحد ایذه، دانشگاه آزاد اسلامی، ایذه، ایران
2 - گروه زیست شناسی، واحد ایذه، دانشگاه آزاد اسلامی، ایذه، ایران
کلید واژه: حافظه, پارکینسون, حرکت, الاژیک اسید,
چکیده مقاله :
ﺑﻴﻤﺎری ﭘﺎرﻛﻴﻨﺴﻮن ﻳﻚ اﺧﺘﻼل ﻧﻮروﭘﺎﺗﻮﻟﻮژﻳﻚ ﺷﺎﻳﻊ اﺳﺖ ﻛﻪ ﺑـﻪ ﻋﻠﺖ دژﻧﺮاﺳﻴﻮن ﻧﻮرون ﻫﺎی دوﭘﺎﻣینرژﻳﻚ ﺑﺨﺶ ﻣﺘﺮاﻛﻢ ﺟﺴﻢ ﺳﻴﺎه اﻳﺠﺎد ﻣﻲ ﺷﻮد. استرس اکسیداتیو به عنوان یک عامل اصلی ایجاد این بیماری محسوب می شود که موجب مرگ نورون ها می شود. ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﺧﺎﺻﻴﺖ آنتی اکسیدانی الاژیک اسید، هدف مطالعه حاضر بررسی اﺛﺮ الاژیک اسید بر اختلالات حرکتی و شناختی در ﻣﺪل حیوانی ﺑﻴﻤﺎری ﭘﺎرﻛﻴﻨﺴﻮن است. چهل سر موش صحرایی نر به پنج گروه هشت تایی تقسیم شدند. به منظور ایجاد مدل حیوانی پارکینسون موش ها، سم عصبی 6- هیدروکسی دوپامین (6-OHDA) را با دوز 8 میکروگرم در 2 میکرولیتر سالین نرمال دارای 01/0 درصد اسید آسکوربیک را درون هسته میانی- قدامی (MFB) سمت چپ مغز دریافت کردند. گروه های درمان الاژیک اسید با دوزهای 10، 25 و 50 میلی گرم بر کیلوگرم را به مدت 14 روز به صورت گاواژ داخل معدی دریافت کردند. یک روز بعد از آخرین گاواژ تست های حرکتی و حافظه از موش ها به عمل آمد. الاژیک اسید باعث بهبود اختلالات حرکتی و حافظه ناشی از پارکینسون بویژه در دوز 50 میلی گرم بر کیلوگرم شد. با توجه به یافته های حاضر در این پژوهش می توان پیشنهاد نمود که الاژیک اسید دارای اﺛـﺮ ﺣﻔﺎﻇﺘﻲ در ﺑﺮاﺑـﺮ 6- ﻫﻴﺪروﻛﺴﻲ دوﭘﺎﻣﻴﻦ در ﻣﺪل ﺗﺠﺮﺑﻲ ﺑﻴﻤﺎری ﭘﺎرﻛﻴﻨﺴﻮن اﺳﺖ.
Parkinson's disease is a prevalent neuropathological disorder induced due to the degeneration of dopaminergic neurons in the dense part of substantia nigra. Oxidative stress is regarded as the main factor of this disease that causes death of neurons. Considering the protective antioxidative property of ellagic acid, the aim of the present study was to investigate the effect of ellagic acid on motor disorders and memory of animal model of Parkinson's disease. Forty male rats were divided into 5 groups. To create an animal model, the rats received 6-OHDA neural poison with dose of 8 µg in 2 µl of normal saline solution with 0.01% of ascorbic acid inside medial forebrain bundle (MFB) on the left side of the brain. The treatment groups received ellagic acid with doses of 10, 25, and 50 mg/kg for 14 d as gastric gavage and tests were conducted on the rats one day after the last gavage. Ellagic acid improves motor and memory disorders motor disorders and memory resulting from Parkinson's disease particularly at doses 50 mg/kg. Considering the present findings, ellagic acid has a protective effect on 6-OHDA in the experimental model of Parkinson's disease.
1. Ascacio-Valdés J.A., Aguilera-Carbó A., Martínez-Hernández J.J., Rodríguez-Herrera R., C.N.A., 2010. Euphorbia antisyphilitica residues as a new source of ellagic acid. Chemical Papers, 64(4): 528- 32.
2. Baluchnejadmojarad T., Roghani M., M. M., 2011. Protective effects of aqueous extract of silybum marianum in 6-hydroxydopamine-induced model of parkinsonism in male rat: a behavioral, biochemical and histological study Koomesh, 12(4): 459-465.
3. Braak H., Rub U., Schultz C., Del Tredici K., 2006. Vulnerability of cortical neurons to Alzheimer's and Parkinson's diseases. Journal of Alzheimer's disease, 9(3): 35-44.
4. Casanova E., Garcia-Mina J.M., Calvo M.I., 2008. Antioxidant and antifungal activity of Verbena officinalis L. leaves. Plant foods for human nutrition, 63(3): 93-97.
5. Chaudhuri K.R., Schapira A.H., 2009. Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment. Lancet neurology, 8(5): 464-474.
6. Chen J.K., Chow S.E., 2005. Antioxidants and myocardial ischemia: reperfusion injuries. Chang Gung Medical Journal, 28(6): 369-377.
7. Choi B.R., Kwon K..J., Park S.H., Jeon W.K., Han S.H., Kim H.Y., 2011. Alternations of Septal-hippocampal System in the Adult Wistar Rat with Spatial Memory Impairments Induced by Chronic Cerebral Hypoperfusion. Experimental Neurobiology, 20(2): 92-99.
8. De Lau L.M., Giesbergen P.C., de Rijk M.C., Hofman A., Koudstaal P.J., Breteler M.M., 2004. Incidence of parkinsonism and Parkinson disease in a general population: the Rotterdam Study. Neurology, 63(7): 1240-1244.
9. Esmaeili A., A.K., 2012. Antioxidant Activity of a Solotion of Thymol in Ethanoal. Zahedan Journal of Researches in Medical Science, 14: 14-18.
10. Franzini L., Ardigo D., Valtuena S., Pellegrini N., Del Rio D., Bianchi M.A., 2012. Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population. Nutrition, Metabolism, and Cardiovascular Diseases, 22(1): 50-57
11. Girish C., Raj V., Arya J., Balakrishnan S., 2013. Involvement of the GABAergic system in the anxiolytic-like effect of the flavonoid ellagic acid in mice. European Journal of Pharmacology, 710(1-3): 49-58
12. Halliwell B., (1995. Antioxidant characterization methodology and mechanisims. Biochemical Pharmacological, 49(10): 1341-1384.
13. Izquierdo I., da Cunha C., Rosat R., Jerusalinsky D., Ferreira M.B., Medina J.H., 1992. Neurotransmitter receptors involved in post-training memory processing by the amygdala, medial septum, and hippocampus of the rat. Behavioral and Neural Biology, 58(1): 16-26.
14. Jankovic J., 2008. Parkinson's disease: clinical features and diagnosis. Journal of Neurology, Neurosurgery, and Psychiatry, 79(4): 368-376.
15. Kirk G.R., White J.S., McKie L., 2006. venson M, Young I, Clements WD, et al. Combined antioxidant therapy reduces pain and improves quality of life in chronic pancreatitis. Journal of gastrointestinal surgery : Official Journal of the Society for Surgery of the Alimentary Tract, 10(4): 499-503.
16. Kordower J.H., Goetz C.G., (1999. The first miracle in neurodegenerative disease: the discovery of oral levodopa. Brain Research Bulletin, 50(5-6): 377-378.
17. Kraus R.L., Pasieczny R., Lariosa-Willingham K., Turner M.S., Jiang A, Trauger J.W., 2005. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity. Journal of Neurochemistry, 94(3) :819-827.
18. Losso J.N., Bansode R.R., Trappey A., 2nd, Bawadi H.A., Truax R., 2004. In vitro anti-proliferative activities of ellagic acid. The Journal of Nutritional Biochemistry, 15(11): 672-678.
19. Lotharius J., Brundin P., 2002. Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. Nature Reviews of Neuroscience, 3(12): 932-942.
20. Martinez J., Moreno J.J., 2000. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochemical pharmacology. 1;59(7):865-70.
21. Nickavar B., Abolhasani F.A., 2009. Screening of antioxidant properties of seven Umbelliferae fruits from Iran. Pakistan Journal of Pharmaceutical Sciences, 22(1): 30-35.
22. Patil D.A., Patil V.A., Bari S.B., Surana S.J., Patil P.O., 2014. Animal Models for Parkinson's Disease. CNS and Neurological Disorders Drug Targets, 13(9):1580-94.
23. Puligheddu M., Figorilli M., Arico D., Raggi A., Marrosu F., Ferri R., 2014. Time structure of leg movement activity during sleep in untreated Parkinson disease and effects of dopaminergic treatment. Sleep Medicine,15(7): 816-824.
24. Rafieirad M., Ghasemzadeh Dehkordi M.L.R., 2014. The Effect of Ellagic Acid on Memory and Pain Induced by Brain Ischemia in Adult Male Rats. ZUMS Journal, 22: 33-42.
25. Sarkaki A., Eidypour Z., Motamedi F., Keramati K., 2012. Motor disturbances and thalamic electrical power of frequency bands' improve by grape seed extract in animal model of Parkinson's disease. Avicenna Journal of Phytomedicine, 2(4): 222-232.
26. Sarkaki A., Norooz Zare F., Farbood Y, A.A. P., 2013. Impaired movements in 6-OHDA induced Parkinson’s rat model improves by pomegranate seed hydroalcoholic extract. Health MED Journal, 7(2): 348-58.
27. Sopala M.., Danysz W., 2001. Chronic cerebral hypoperfusion in the rat enhances age-related deficits in spatial memory. Journal of Neural Transmission, 108(12): 1445-1456.
28. Spencer W.A., Jeyabalan J., Kichambre S., Gupta R.C., 2011. Oxidatively generated DNA damage after Cu(II) catalysis of dopamine and related catecholamine neurotransmitters and neurotoxins: Role of reactive oxygen species. Free Radical Biology and Medicine, 50(1): 139-147.
29. Storch A., Ott S., Hwang Y.I., Ortmann R., Hein A., Frenzel S., 2002. Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson's disease: studies using heterologous expression systems of the dopamine transporter. Biochemical Pharmacology, 63(5): 909-920.
30. Tamburella A., Micale V., Mazzola C., Salomone S., Drago F., 2012. The selective norepinephrine reuptake inhibitor atomoxetine counteracts behavioral impairments in trimethyltin-intoxicated rats. European Journal of Pharmacology, 683(1-3): 148-154.
31. Tarawneh R., Galvin J.E., 2010. Potential future neuroprotective therapies for neurodegenerative disorders and stroke. Clinics in Geriatric Medicine, 26(1): 125-147.
32. Thakur K., KS P., 2008. Polarographic (DCP & DPP) Determination of Ellagic Acid in Strawberries & Pharmaceutical Formulations. Journal of Chinese Chemical Society, 55: 143-146.
33. Uzar E., Acar A., Evliyaoglu O., Firat U., Kamasak K., Gocmez C., 2012. The anti-oxidant and anti-apoptotic effects of nebivolol and zofenopril in a model of cerebral ischemia/reperfusion in rats. Progress in Neuro-psychopharmacology and Biological Psychiatry, 36(1): 22-28.
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