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Cerebroprotective potential of resveratrol through anti-oxidant and anti-inflammatory mechanisms in rats

  • Neurology and Preclinical Neurological Studies - Original Article
  • Published:
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Abstract

Oxidative stress and inflammation are two important pathological mechanisms involved in cerebral ischemia and reperfusion injury. In pathological conditions such as cerebral infarction, the free radical production is greater than that of elimination by endogenous anti-oxidant system, by this undesirable effect brain is highly injured. Resveratrol is reported to have anti-oxidant and anti-inflammatory, athero-protective activities. Therefore, the aim of the present study is to evaluate the therapeutic potential of resveratrol against cerebral infarction induced by ischemia and reperfusion injury in Wistar rats. Bi-common carotid occlusion followed by 4 h reperfusion model was used to induce cerebral infarction. Percent infarction, oxidative stress markers (malondialdehyde, catalase, superoxide dismutase) and inflammatory markers (myeloperoxidase, TNF-α, IL-6, ICAM-1 and IL-10) were measured. TNF-α, IL-6, IL-10, and intracellular adhesive molecule-I (ICAM-1) levels were quantified by enzyme-linked immunosorbent assay (ELISA). Resveratrol produced significant dose-dependent reduction in percent cerebral infarct volume. At resveratrol 20 mg/kg dose, there was a significant reduction in oxidative stress and inflammatory markers like malondialdehyde, TNF-α, IL-6, myeloperoxidase and ICAM-I and in contrast there was a significant increase in anti-oxidants and anti-inflammatory markers like superoxide dismutase, catalase and IL-10 levels. Resveratrol showed significant cerebroprotective action mediated by anti-oxidant and anti-inflammatory mechanisms.

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References

  • Aebi H (1974) Catalase: methods in enzymatic analysis Vol.II (ed.H.U.Bergmer) 673–84

  • Aggarwal BB, Bhardwai A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y (2004) Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res 24(5A):2783–27840

    CAS  PubMed  Google Scholar 

  • Alarcon de la Lastra C, Villegas I (2007) Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem Soc Trans 35:1156–1160

    Article  CAS  PubMed  Google Scholar 

  • Andrabi SA, Spina MG, Lorenz P, Ebmeyer U, Wolf G, Horn TF (2004) Oxyresveratrol (trans-2, 3′, 4, 5′- tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia. Brain Res 1017:98–107

    Article  CAS  PubMed  Google Scholar 

  • Ban JY, Cho SO, Choi SH, Ju HS, Kim JY, Bae K, Song KS, Seong YH (2008) Neuroprotective effect of Smilacis chinae rhizome on NMDA-induced neurotoxicity in vitro and focal cerebral ischemia in vivo. J Pharmacol Sci 106(1):68–77

    Article  CAS  PubMed  Google Scholar 

  • Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H (1986) Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 17:472–476

    Article  CAS  PubMed  Google Scholar 

  • Bruning CA, Prigol M, Luchese C, Jesse CR, Duarte MM, Roman SS, Nogueria CW (2012) Protective effect of diphenyl diselenide on ischemia and reperfusion-induced cerebral injury: involvement of oxidative stress and pro-inflammatory cytokines. Neurochem Res (Epub ahead of print)

  • Chanvitayapongs S, Draczynska LB, Sun AY (1997) Amelioration of oxidative stress by antioxidant and resveratrol in PC12 cells. Neuroreport 8:1499–1502

    Article  CAS  PubMed  Google Scholar 

  • Dawn B (2007) Resveratrol: ready for prime time? J Mol Cell Cardiol 42(3):484–486

    Article  CAS  PubMed  Google Scholar 

  • Del Zoppo GJ (1997) Microvascular responses to cerebral ischemia/inflammation. Ann NY Acad Sci 823:132–147

    Article  PubMed  Google Scholar 

  • Della-Morte D, Dave KR, DeFazio RA, Bao YC, Raval AP, Perez-Pinzon MA (2009) Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway. Neuroscience 159:993–1002

    Article  CAS  PubMed  Google Scholar 

  • Donnan GA, Fisher M, Macleod M, Davis SM (2008) Stroke. Lancet 371:1612–1623

    Article  CAS  PubMed  Google Scholar 

  • Frank PG, Lisanti MP (2008) ICAM-1: role in inflammation and in the regulation of vascular permeability. Am J Physiol Heart Circ Physiol 295(3):H926–H927

    Article  CAS  PubMed  Google Scholar 

  • Hakim J (1993) Reactive oxygen species and inflammation. CR Seances Soc Biol Fil 187(3):286–295

    CAS  Google Scholar 

  • Iwasaki Y, Ito S, Suzuki M, Nagahori T, Yamamato T, Konno H (1989) Forebrain ischemia induced by temporary bilateral common carotid occlusion in normotensive rats. J Neurol Sci 90:155–165

    Article  CAS  PubMed  Google Scholar 

  • Juhasz B, Varga B, Gesztelyi R, Kemeny-Beke A, Zsuga J, Tosaki A (2010) Resveratrol: a multifunctional cytoprotective molecule. Curr Pharm Biotechnol 11(8):810–818

    Article  CAS  PubMed  Google Scholar 

  • Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Ind J Bio Chem Biophys 21(2):130–132

    CAS  Google Scholar 

  • Kaste M (1997) Current therapeutic options for brain ischemia. Neurology 49:s56–s59

    Article  CAS  PubMed  Google Scholar 

  • Keller JN, Kindy MS, Holtsberg FW et al (1998) Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J Neurosci 18(2):687–697

    CAS  PubMed  Google Scholar 

  • Khan M, Siphon B, Jatana M, Giri S, Gilg AG, Sekhon C, Singh AK (2004) Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. J Neurosci Res 76(4):519–527

    Article  CAS  PubMed  Google Scholar 

  • Kim HK (1997) Experimental models of cerebral ischemia. Acta Anaesthesiol Scand Suppl 111:91–92

    CAS  PubMed  Google Scholar 

  • Kumar P, Padi SS, Naidu PS, Kumar A (2006) Effect of resveratrol on 3-nitropropionic acid-induced biochemical and behavioral changes: possible neuroprotective mechanisms. Behav Pharmacol 17:485–492

    Article  CAS  PubMed  Google Scholar 

  • Lakhan SE, Kirchgessner A, Hfer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 7:97

    Article  PubMed  Google Scholar 

  • Lanzillotta A, Sarnico I, Ingrassia R et al (2010) The acetylation of RelA in Lys310 dictates the NF-κB-dependent response in post-ischemic injury. Cell Death Dis 1:e96

    Article  CAS  PubMed  Google Scholar 

  • Lapi D, Vagnani S, Pignataro G, Esposito E, Paterni M, Colantuoni A (2012) Rat Pial microvascular responses to transient bilateral common carotid artery occlusion and reperfusion: Quercetin’s mechanism of action. Front Physiol 3:99

    CAS  PubMed  Google Scholar 

  • Liu N, Chen R, Du H, Wang J, Zhang Y, Wen J (2009) Expression of IL-10 and TNF-alpha in rats with cerebral infarction after transplantation with mesenchymal stem cells. Cell Mol Immunol 6:207–213

    Article  PubMed  Google Scholar 

  • Liu C, Shi Z, Fan L, Chen Z, Wang K, Wang B (2011) Resveratrol improves neuron protection and functional recovery in rat model of spinal cord injury. Brain Res 1374:100–109

    Article  CAS  PubMed  Google Scholar 

  • Markus MA, Morris BJ (2008) Resveratrol in prevention and treatment of common clinical conditions of aging. Clin Interv Aging 3(2):331–339

    CAS  PubMed  Google Scholar 

  • Mohagheghi F, Khalaj L, Ahmadiani A, Rahmani B (2012) 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 (Epub ahead of print)

  • Mukherjee PK, Ahamed KF, Kumar V, Mukherjee K, Houghton PJ (2007) Protective effect of biflavones from Araucaria bidwillii Hook in rat cerebral ischemia/reperfusion induced oxidative stress. Behav Brain Res 178:221–228

    Article  CAS  PubMed  Google Scholar 

  • Mullane KM, Bruce Smith ND (1985) Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into lschemic myocardium. J Pharmacol Methods 14:157–167

    Article  CAS  PubMed  Google Scholar 

  • Nassar NN, Abdelsalam RM, Abdel-Rahman AA, Abdallah DM (2012) 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(3):614–621

    Article  CAS  PubMed  Google Scholar 

  • Okhawa H, Ohishi N, Yagi K (1979) Assay of lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  Google Scholar 

  • Park JS, Kim KM, Kim MH, Chang HJ, Baek MK (2009) Resveratrol inhibits tumor cell adhesion to endothelial cells by blocking ICAM-1 expression. Anticancer Res 29(1):355–362

    CAS  PubMed  Google Scholar 

  • Rahman A, Bando M, Kefer J, Anwar KN, Malik AB (1999) Protein kinase C-activated oxidant generation in endothelial cells signals intercellular adhesion molecule-1 gene transcription. Mol Pharmacol 55(3):575–583

    CAS  PubMed  Google Scholar 

  • Saito K, Suyama K, Nishida K, Sei Y, Basile AS (1996) Early increases in TNF-alpha, IL-6 and IL-1 beta following transient cerebral ischemia in gerbil brain. Neurosci Lett 206:149–152

    Article  CAS  PubMed  Google Scholar 

  • Sinha K, chaudhary G, Gupta YK (2002) Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sci 71:655–665

    Article  CAS  PubMed  Google Scholar 

  • Slemmer JE, Shacka JJ, Sweeney MI, Weber JT (2008) Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem 15(4):404–414

    Article  CAS  PubMed  Google Scholar 

  • Solaroglu I, Solaroglu A, Kaptanoglu E, Dede S, Haberal A, Beskonakli E, Kilinc K (2003) Erythropoietin prevents ischemia-reperfusion from inducing oxidative damage in fetal rat brain. Childs Nerv Syst 19:19–22

    PubMed  Google Scholar 

  • Thirunavukkarasu M, Penumathsa SV, Koneru S et al (2007) Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: role of nitric oxide, thioredoxin, and heme oxygenase. Free Radic Biol Med 43(5):720–729

    Article  CAS  PubMed  Google Scholar 

  • Tosaki A, Koltai M, Joo F, Adam G et al (1985) Actinomycin D suppresses the protective effect of dexamethasone in rats affected by global cerebral ischemia. Stroke 16(3):501–505

    Article  CAS  PubMed  Google Scholar 

  • Tosaki A, Szerdahelyi P, Joo F (1994) Treatment with ranitidine of ischemic brain edema. Eur J Pharmacol 264(3):455–458

    Article  CAS  PubMed  Google Scholar 

  • Vidavalur R, Otani H, Singal PK, Singal MN (2006) Significance of wine and resveratrol in cardiovascular disease: French paradox revisited. Exp Clin Cardiol 11(3):217–225

    CAS  PubMed  Google Scholar 

  • Virgili M, Contestabile A (2000) Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans resveratrol in rats. Neurosci Lett 281(2–3):123–126

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Xu J, Rottinghaus GE, Simonyi A, Lubahn D, Sun GY, Sun AY (2002) Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res 958(2):439–447

    Article  CAS  PubMed  Google Scholar 

  • Wong CH, Crack PJ (2008) Modulation of neuro-inflammation and vascular response by oxidative stress following cerebral ischemia–reperfusion injury. Curr Med Chem 15(1):1–14

    Article  CAS  PubMed  Google Scholar 

  • Yousuf S, Atif F, Ahmad M, Hoda MN, Khan MB, Ishrat T, Islam F (2007) Selenium plays a modulatory role against cerebral ischemia-induced neuronal damage in rat hippocampus. Brain Res 1147:218–225

    Article  CAS  PubMed  Google Scholar 

  • Yousuf S, Atif F, Ahmad M, Hoda N, Ishrat T, Khan B, Islam F (2009) Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia. Brain Res 1250:242–253

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Liu J, Shi JS (2010) Anti-inflammatory activities of resveratrol in the brain: role of resveratrol in microglial activation. Eur J Pharmacol 636:1–7

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Srinivasarao College of Pharmacy, P.M.Palem, Visakhapatnam, Andhra Pradesh, 530041, India

    Prabhakar Orsu

  2. Govt. Polytechnic College for Women, Srikakulam, India

    B. V. S. N. Murthy

  3. A.U. College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, 5300003, India

    Annapurna Akula

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  1. Prabhakar Orsu
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  2. B. V. S. N. Murthy
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  3. Annapurna Akula
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Correspondence to Prabhakar Orsu.

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Orsu, P., Murthy, B.V.S.N. & Akula, A. Cerebroprotective potential of resveratrol through anti-oxidant and anti-inflammatory mechanisms in rats. J Neural Transm 120, 1217–1223 (2013). https://doi.org/10.1007/s00702-013-0982-4

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  • DOI: https://doi.org/10.1007/s00702-013-0982-4

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