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http://dx.doi.org/10.3340/jkns.2015.58.6.508

Neuroprotective Effect of Resveratrol on Acute Brain Ischemia Reperfusion Injury by Measuring Annexin V, p53, Bcl-2 Levels in Rats  

Kizmazoglu, Ceren (Department of Neurosurgery, Katip Celebi University Izmir Ataturk Training and Research Hospital)
Aydin, Hasan Emre (Department of Neurosurgery, Eskisehir State Hospital)
Sevin, Ismail Ertan (Department of Neurosurgery, Katip Celebi University Izmir Ataturk Training and Research Hospital)
Kalemci, Orhan (Department of Neurosurgery, Dokuz Eylul University, School of Medicine Hospital)
Yuceer, Nurullah (Department of Neurosurgery, Katip Celebi University Izmir Ataturk Training and Research Hospital)
Atasoy, Metin Ant (Department of Neurosurgery, Eskisehir Osmangazi University School of Medicine Hospital)
Publication Information
Journal of Korean Neurosurgical Society / v.58, no.6, 2015 , pp. 508-512 More about this Journal
Abstract
Background : Cerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V. Methods : We preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001. Results : After administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups. Conclusion : In the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53.
Keywords
Resveratrol; Brain Ischemia; Annexin V; Bcl-2; p53;
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1 Aboutaleb N, Shamsaei N, Khaksari M, Erfani S, Rajabi H, Nikbakht F : Pre-ischemic exercise reduces apoptosis in hippocampal CA3 cells after cerebral ischemia by modulation of the Bax/Bcl-2 proteins ratio and prevention of caspase-3 activation. J Physiol Sci 65 : 435-443, 2015   DOI
2 Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y : Role of resveratrol in prevention and therapy of cancer : preclinical and clinical studies. Anticancer Res 24 (5A) : 2783-2840, 2004
3 Choi SK, Lee GJ, Choi S, Kim YJ, Park HK, Park BJ : Neuroprotective effects by nimodipine treatment in the experimental global ischemic rat model : real time estimation of glutamate. J Korean Neurosurg Soc 49 : 1-7, 2011   DOI
4 de la Lastra CA, Villegas I : Resveratrol as an antioxidant and pro-oxidant agent : mechanisms and clinical implications. Biochem Soc Trans 35 (Pt 5) : 1156-1160, 2007   DOI
5 del Zoppo GJ : Microvascular responses to cerebral ischemia/inflammation. Ann N Y Acad Sci 823 : 132-147, 1997   DOI
6 Di Carlo A : Human and economic burden of stroke. Age Ageing 38 : 4-5, 2009
7 Donnan GA, Fisher M, Macleod M, Davis SM : Stroke. Lancet 371 : 1612-1623, 2008   DOI
8 Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E : Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 322 : 254-262, 2012   DOI
9 Green DR, Chipuk JE : p53 and metabolism : inside the TIGAR. Cell 126 : 30-32, 2006   DOI
10 Iwasaki Y, Ito S, Suzuki M, Nagahori T, Yamamoto T, Konno H : Forebrain ischemia induced by temporary bilateral common carotid occlusion in normotensive rats. J Neurol Sci 90 : 155-165, 1989   DOI
11 Juhasz B, Varga B, Gesztelyi R, Kemeny-Beke A, Zsuga J, Tosaki A : Resveratrol : a multifunctional cytoprotective molecule. Curr Pharm Biotechnol 11 : 810-818, 2010   DOI
12 Kaburaki J, Kuwana M, Yamamoto M, Kawai S, Ikeda Y : Clinical significance of anti-annexin V antibodies in patients with systemic lupus erythematosus. Am J Hematol 54 : 209-213, 1997   DOI
13 Lee KO, Kim WJ, Na SJ, Heo JH, Lee KY : Clinical significance of anti-annexin V antibody in acute cerebral ischemia. J Neurol Sci 305 : 53-56, 2011   DOI
14 Khan M, Sekhon B, Jatana M, Giri S, Gilg AG, Sekhon C, et al. : Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. J Neurosci Res 76 : 519-527, 2004   DOI
15 Lahiry L, Saha B, Chakraborty J, Bhattacharyya S, Chattopadhyay S, Banerjee S, et al. : Contribution of p53-mediated bax transactivation in theaflavin-induced mammary epithelial carcinoma cell apoptosis. Apoptosis 13 : 771-781, 2008   DOI
16 Lakhan SE, Kirchgessner A, Hofer M : Inflammatory mechanisms in ischemic stroke : therapeutic approaches. J Transl Med 7 : 97, 2009   DOI
17 Li C, Yan Z, Yang J, Chen H, Li H, Jiang Y, et al. : Neuroprotective effects of resveratrol on ischemic injury mediated by modulating the release of neurotransmitter and neuromodulator in rats. Neurochem Int 56 : 495-500, 2010   DOI
18 Li H, Yan Z, Zhu J, Yang J, He J : Neuroprotective effects of resveratrol on ischemic injury mediated by improving brain energy metabolism and alleviating oxidative stress in rats. Neuropharmacology 60 : 252-258, 2011   DOI
19 Li Z, Pang L, Fang F, Zhang G, Zhang J, Xie M, et al. : Resveratrol attenuates brain damage in a rat model of focal cerebral ischemia via up-regulation of hippocampal Bcl-2. Brain Res 1450 : 116-124, 2012   DOI
20 Lieberthal W, Menza SA, Levine JS : Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. Am J Physiol 274 (2 Pt 2) : F315-F327, 1998
21 Mahajan NP, Linder K, Berry G, Gordon GW, Heim R, Herman B : Bcl-2 and bax interactions in mitochondria probed with green fluorescent protein and fluorescence resonance energy transfer. Nat Biotechnol 16 : 547-552, 1998   DOI
22 Love S : Apoptosis and brain ischaemia. Prog Neuropsychopharmacol Biol Psychiatry 27 : 267-282, 2003   DOI
23 Lu X, Xu H, Sun B, Zhu Z, Zheng D, Li X : Enhanced neuroprotective effects of resveratrol delivered by nanoparticles on hydrogen peroxide-induced oxidative stress in rat cortical cell culture. Mol Pharm 10 : 2045-2053, 2013   DOI
24 Mackay J, Mensah GA, Mendis S, Greenlund K : The atlas of heart disease and stroke. Geneva : World Health Organization, 2004
25 Markus MA, Morris BJ : Resveratrol in prevention and treatment of common clinical conditions of aging. Clin Interv Aging 3 : 331-339, 2008
26 Mohagheghi F, Khalaj L, Ahmadiani A, Rahmani B : Gemfibrozil pretreatment affecting antioxidant defense system and inflammatory, but not Nrf-2 signaling pathways resulted in female neuroprotection and male neurotoxicity in the rat models of global cerebral ischemia-reperfusion. Neurotox Res 23 : 225-237, 2013   DOI
27 Molchadsky A, Shats I, Goldfinger N, Pevsner-Fischer M, Olson M, Rinon A, et al. : p53 plays a role in mesenchymal differentiation programs, in a cell fate dependent manner. PLoS One 3 : e3707, 2008   DOI
28 Mukherjee PK, Ahamed KF, Kumar V, Mukherjee K, Houghton PJ : Protective effect of biflavones from araucaria bidwillii hook in rat cerebral ischemia/reperfusion induced oxidative stress. Behav Brain Res 178 : 221-228, 2007   DOI
29 Orsu P, Murthy BV, Akula A : Cerebroprotective potential of resveratrol through anti-oxidant and anti-inflammatory mechanisms in rats. J Neural Transm 120 : 1217-1223, 2013   DOI
30 Nassar NN, Abdelsalam RM, Abdel-Rahman AA, Abdallah DM : Possible involvement of oxidative stress and inflammatory mediators in the protective effects of the early preconditioning window against transient global ischemia in rats. Neurochem Res 37 : 614-621, 2012   DOI
31 Park HS, Han KH, Shin JA, Park JH, Song KY, Kim DH : The neuroprotective effects of carnosine in early stage of focal ischemia rodent model. J Korean Neurosurg Soc 55 : 125-130, 2014   DOI
32 Pathak D, Berthet A, Nakamura K : Energy failure : does it contribute to neurodegeneration? Ann Neurol 74 : 506-516, 2013   DOI
33 Phillis JW, O'Regan MH : Characterization of modes of release of amino acids in the ischemic/reperfused rat cerebral cortex. Neurochem Int 43 : 461-467, 2003   DOI
34 Prabhakar O : Cerebroprotective effect of resveratrol through antioxidant and anti-inflammatory effects in diabetic rats. Naunyn Schmiedebergs Arch Pharmacol 386 : 705-710, 2013   DOI
35 Qin ZH, Chen RW, Wang Y, Nakai M, Chuang DM, Chase TN : Nuclear factor kappaB nuclear translocation upregulates c-Myc and p53 expression during NMDA receptor-mediated apoptosis in rat striatum. J Neurosci 19 : 4023-4033, 1999   DOI
36 Rami A : Ischemic neuronal death in the rat hippocampus : the calpain-calpastatin-caspase hypothesis. Neurobiol Dis 13 : 75-88, 2003   DOI
37 Slemmer JE, Shacka JJ, Sweeney MI, Weber JT : Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem 15 : 404-414, 2008   DOI
38 Raynal P, Pollard HB : Annexins : the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins. Biochim Biophys Acta 1197 : 63-93, 1994   DOI
39 Shin JA, Lee KE, Kim HS, Park EM : Acute resveratrol treatment modulates multiple signaling pathways in the ischemic brain. Neurochem Res 37 : 2686-2696, 2012   DOI
40 Sinha K, Chaudhary G, Gupta YK : Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sci 71 : 655-665, 2002   DOI
41 Steckley D, Karajgikar M, Dale LB, Fuerth B, Swan P, Drummond-Main C, et al. : Puma is a dominant regulator of oxidative stress induced bax activation and neuronal apoptosis. J Neurosci 27 : 12989-12999, 2007   DOI
42 van Heerde WL, Poort S, van't Veer C, Reutelingsperger CP, de Groot PG : Binding of recombinant annexin V to endothelial cells : effect of annexin V binding on endothelial-cell-mediated thrombin formation. Biochem J 302 (Pt 1) : 305-312, 1994   DOI
43 Vidavalur R, Otani H, Singal PK, Maulik N : Significance of wine and resveratrol in cardiovascular disease : French paradox revisited. Exp Clin Cardiol 11 : 217-225, 2006
44 Wang Q, Xu J, Rottinghaus GE, Simonyi A, Lubahn D, Sun GY, et al. : Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res 958 : 439-447, 2002   DOI
45 Yilmaz MB, Tonge M, Emmez H, Kaymaz F, Kaymaz M : Neuroprotective effects of quetiapine on neuronal apoptosis following experimental transient focal cerebral ischemia in rats. J Korean Neurosurg Soc 54 : 1-7, 2013   DOI
46 Warlow C, Sudlow C, Dennis M, Wardlaw J, Sandercock P : Stroke. Lancet 362 : 1211-1224, 2003   DOI
47 White BC, Sullivan JM, DeGracia DJ, O'Neil BJ, Neumar RW, Grossman LI, et al. : Brain ischemia and reperfusion : molecular mechanisms of neuronal injury. J Neurol Sci 179 (S 1-2) : 1-33, 2000   DOI
48 Wong CH, Crack PJ : Modulation of neuro-inflammation and vascular response by oxidative stress following cerebral ischemia-reperfusion injury. Curr Med Chem 15 : 1-14, 2008   DOI
49 Zhang F, Liu J, Shi JS : Anti-inflammatory activities of resveratrol in the brain : role of resveratrol in microglial activation. Eur J Pharmacol 636 : 1-7, 2010   DOI
50 Zheng JP, Ju D, Jiang H, Shen J, Yang M, Li L : Resveratrol induces p53 and suppresses myocardin-mediated vascular smooth muscle cell differentiation. Toxicol Lett 199 : 115-122, 2010   DOI