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Journal of Chinese Integrative Medicine ›› 2013, Vol. 11 ›› Issue (5): 337-342.doi: 10.3736/jintegrmed2013042

• Research Article • Previous Articles     Next Articles

Effects of rutin on oxidative stress in mice with kainic acid-induced seizure

Marjan Nassiri-Asla(), Taghi Naserpour Farivarb, Esmail Abbasic, Hamid Reza Sadeghniad, Mehdi SheikhieMina Lotfizadehf, Parisa Bazahangf   

  1. a. Cellular and Molecular Research Centre, Department of Pharmacology, Qazvin University of Medical Sciences, Qazvin, Iran
    b. Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran
    c. Department of Pharmacology, Qazvin University of Medical Sciences, Qazvin, Iran
    d. Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad,Iran
    e. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
    f. School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
  • Received:2013-03-04 Accepted:2013-05-27 Online:2013-09-10 Published:2013-09-15

Objective

Flavonoids are present in foods such as fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich foods and prevention of human disease, including neurodegenerative disorders. We assessed the effect of rutin (quercetin-3-O-rutinoside) on oxidative stress in kainic acid (KA)-induced seizure.


Methods

Thirty-six BALB/c mice were randomly divided into three groups. In the control group, saline (intra-peritoneal, i.p.) was administered for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of saline. In rutin groups, mice were pretreated with rutin (100 and 200 mg/kg, i.p.) for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of rutin. Subsequently, behavioural changes were observed in mice. Lipid peroxidation and oxidative stress were measured respectively in the early and late phases after KA-induced seizures.


Results

Seizure scores in the rutin groups were significantly lower than those in the control group (P < 0.01). Furthermore, rutin dose-dependently inhibited the number of wet-dog shakes (WDS) (P<0.05). Malondialdehyde level in the hippocampus of the rutin groups was significantly lower than that in the hippocampus of the control group on days 1 and 21 after KA administration. In the rutin groups, the thiol levels observed on day 1 after KA administration were highe+r than that in the control group (P < 0.01).


Conclusion

These results indicate that rutin has potential anticonvulsant and antioxidative activities against oxidative stress in KA-induced seizure in mice.

Key words: Plant extracts, Rutin, Kainic acid, Oxidative stress, Epilepsy, Seizure, Mice

Figure 1

The effects of rutin (100 and 200 mg/kg) on seizure score (A), onset of WDS (B) and the number of WDS (C) in mice with KA-induced seizure The control group was administered saline (i.p.) for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of saline. Rutin (100 and 200 mg/kg, i.p.) was administered for 7 d, and on the last day KA (10 mg/ kg, i.p.) was injected 30 min after the administration of rutin. Data are expressed as mean ± standard error of mean. *P < 0.05, **P < 0.01, vs control group, n=36, analyzed by post-hoc Tukey’s test. KA: kainic acid; WDS: wet-dog shake."

Figure 2

Effect of rutin on MDA in the hippocampus on days 1 and 21 after kainic acid administration Values are expressed as mean ± standard error of mean. *P < 0.05, **P < 0.01, vs control group, n=6, analyzed by post-hoc Tukey’s test. MDA: malondialdehyde."

Figure 3

Effect of rutin on total thiol concentrations in the hippocampus on days 1 and 21 after kainic acid administrationValues are expressed as mean ± standard error of mean. **P < 0.01, compared to control group, n=6, analyzed by post-hoc Tukey’s test."

[1] Simon RP, Greenberg DA, Aminof MJ . Clinical neurology.7th ed[M]. New York: McGraw-Hill Companies, Inc, 2009,272
[2] Gupta YK, Briyal S . Protective effect of vineatrol against kainic acid induced seizures, oxidative stress and on the expression of heat shock proteins in rats[J]. Eur Neuropsycho-pharmacol, 2006,16(2):85-91
doi: 10.1016/j.euroneuro.2005.07.004
[3] Yalcin A, Kilinc E, Kocturk S, Resmi H, Sozmen EY . Effect of melatonin cotreatment against kainic acid on coenzyme Q10, lipid peroxidation and Trx mRNA in rat hippocampus[J]. Int J Neurosci, 2004,114(9):1085-1897
doi: 10.1080/00207450490475535
[4] Shin HJ, Lee JY, Son E, Lee DH, Kim HJ, Kang SS, Cho GJ, Choi WS, Roh GS . Curcumin attenuates the kainic acid-induced hippocampal cell death in the mice[J]. Neurosci Lett, 2007,416(1):49-54
doi: 10.1016/j.neulet.2007.01.060
[5] Ben-Ari Y, Cossart R . Kainate, a double agent that generates seizures: two decades of progress[J]. Trends Neurosci, 2000,23(11):580-587
doi: 10.1016/S0166-2236(00)01659-3
[6] Liang LP, Ho YS, Patel M . Mitochondrial superoxide production in kainate-induced hippocampal damage[J]. Neuroscience, 2000,101(3):563-570
doi: 10.1016/S0306-4522(00)00397-3
[7] Won SJ, Ko HW, Kim EY, Park EC, Huh K, Jung NP, Choi I, Oh YK, Shin HC, Gwag BJ . Nuclear factor κB-mediated kainate neurotoxicity in the rat and hamster hippocampus[J]. Neuroscience, 1999,94(1):83-91
doi: 10.1016/S0306-4522(99)00196-7
[8] Gupta YK, Briyal S, Chaudhary G . Protective effect of trans-resveratrol against kainic acid-induced seizures and oxidative stress in rats[J]. Pharmacol Biochem Behav, 2002,71(1-2):245-249
doi: 10.1016/S0091-3057(01)00663-3
[9] Kunti? V, Peji? N, Ivkovi? B, Vuji? Z, Ili? K, Mi?i? S, Vukojevi? V . Isocratic RP-HPLC method for rutin determination in solid oral dosage forms[J]. J Pharm Biomed Anal, 2007,43(2):718-721
doi: 10.1016/j.jpba.2006.07.019
[10] Marks SC, Mullen W, Borges G, Crozier A . Absorption, metabolism, and excretion of cider dihydrochalcones in healthy humans and subjects with an ileostomy[J]. J Agric Food Chem, 2009,57(5):2009-2015
doi: 10.1021/jf802757x
[11] Trumbeckaite S, Bernatoniene J, Majiene D, Jakstas V, Savickas A, Toleikis A . The effect of flavonoids on rat heart mitochondrial function[J]. Biomed Pharmacother, 2006,60(5):245-248
[12] Pu F, Mishima K, Irie K, Motohashi K, Tanaka Y, Orito K, Egawa T, Kitamura Y, Egashira N, Iwasaki K, Fujiwara M . Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats[J]. J Pharmacol Sci, 2007,104(4):329-334
doi: 10.1254/jphs.FP0070247
[13] Richetti SK, Blank M, Capiotti KM, Piato AL, Bogo MR, Vianna MR, Bonan CD . Quercetin and rutin prevent scopolamine-induced memory impairment in zebrafish[J]. Behav Brain Res, 2011,217(1):10-15
doi: 10.1016/j.bbr.2010.09.027
[14] Javed H, Khan MM, Ahmad A, Vaibhav K, Ahmad ME, Khan A, Ashafaq M, Islam F, Siddiqui MS, Safhi MM, Islam F . Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type[J]. Neuroscience, 2012,210:340-352
doi: 10.1016/j.neuroscience.2012.02.046
[15] Gupta R, Singh M, Sharma A . Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury[J]. Pharmacol Res, 2003,48(2):209-215
doi: 10.1016/S1043-6618(03)00102-6
[16] Khan MM, Ahmad A, Ishrat T, Khuwaja G, Srivastawa P, Khan MB, Raza SS, Javed H, Vaibhav K, Khan A, Islam F . Rutin protects the neural damage induced by transient focal ischemia in rats[J]. Brain Res, 2009,1292:123-135
doi: 10.1016/j.brainres.2009.07.026
[17] Rockhold RW, Jin C, Huang HM, Farley JM . Acute tachycardia and pressor effects following injections of kainic acid into the antero-dorsal medial hypothalamus[J]. Neuropharmacology, 1987,26(6):567-573
doi: 10.1016/0028-3908(87)90149-3
[18] Golechha M, Chaudhry U, Bhatia J, Saluja D, Arya DS . Naringin protects against kainic acid-induced status epilepticus in rats: evidence for an antioxidant, anti-inflammatory and neuroprotective intervention[J]. Biol Pharm Bull, 2011,34(3):360-365
doi: 10.1248/bpb.34.360
[19] Morrison RS, Wenzel HJ, Kinoshita Y, Robbins CA, Donehower LA, Schwartzkroin PA . Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death[J]. J Neurosci, 1996,16(4):1337-1345
doi: 10.1523/JNEUROSCI.16-04-01337.1996
[20] Shin EJ, Jeong JH, Kim AY, Koh YH, Nah SY, Kim WK, Ko KH, Kim HJ, Wie MB, Kwon YS, Yoneda Y, Kim HC . Protection against kainate neurotoxicity by ginsenosides: attenuation of convulsive behavior, mitochondrial dysfunction, and oxidative stress[J]. J Neurosci Res, 2009,87(3):710-722
doi: 10.1002/jnr.v87:3
[21] López-Meraz ML, González-Trujano ME, Neri-Bazán L, Hong E, Rocha LL . 5-HT1A receptor agonists modify epileptic seizures in three experimental models in rats[J]. Neuropharmacology, 2005,49(3):367-375
doi: 10.1016/j.neuropharm.2005.03.020
[22] Shin EJ, Ko KH, Kim WK, Chae JS, Yen TP, Kim HJ, Wie MB, Kim HC . Role of glutathione peroxidase in the ontogeny of hippocampal oxidative stress and kainate seizure sensitivity in the genetically epilepsy-prone rats[J]. Neurochem Int, 2008,52(6):1134-1147
doi: 10.1016/j.neuint.2007.12.003
[23] Janero DR . Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury[J]. Free Radic Biol Med, 1990,9(6):515-540
doi: 10.1016/0891-5849(90)90131-2
[24] Ellman GL . Tissue sulfhydryl groups[J]. Arch Biochem Biophys, 1959,82(1):70-77
doi: 10.1016/0003-9861(59)90090-6
[25] Hosseinzadeh H, Taiari S, Nassiri-Asl M . Effect of thymoquinone, a constituent of Nigella sativa L., on ischemia-reperfusion in rat skeletal muscle[J]. Naunyn-Schmiedebergs Arch Pharmacol, 2012,385(5):503-508
doi: 10.1007/s00210-012-0726-2
[26] Rodrigues MC, Rossetti F, Foresti ML, Arisi GM, Furtado MA, Dal-Cól ML, Bertti P, Fernandes A, Santos FL, Del Vecchio F, Garcia-Cairasco N . Correlation between shaking behaviors and seizure severity in five animal models of convulsive seizures[J]. Epilepsy Behav, 2005,6(3):328-336
doi: 10.1016/j.yebeh.2005.02.005
[27] Shin C, Pedersen HB , McNamara JO.γ-Aminobutyric acid and benzodiazepine receptors in the kindling model of epilepsy: a quantitative radio histochemical study[J]. J Neurosci, 1985,5(10):2696-2701
doi: 10.1523/JNEUROSCI.05-10-02696.1985
[28] Nassiri-Asl M, Shariati-Rad S, Zamansoltani F . Anticonvulsive effects of intracerebroventricular administration of rutin in rats[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2008,32(4):989-993
doi: 10.1016/j.pnpbp.2008.01.011
[29] Nassiri-Asl M, Mortazavi SR, Samiee-Rad F, Zangivand AA, Safdari F, Saroukhani S, Abbasi E . The effects of rutin on the development of pentylenetetrazole kindling and memory retrieval in rats[J]. Epilepsy Behav, 2010,18(1-2):50-53
doi: 10.1016/j.yebeh.2010.03.005
[30] Marder M, Paladini AC . GABAA-receptor ligands of ?avonoid structure[J]. Curr Top Med Chem, 2002,2(8):853-867
doi: 10.2174/1568026023393462
[31] Medina JH, Viola H, Wolfman C, Marder M, Wasowski C, Calvo D, Paladini AC . Overview — ?avonoids: a new family of benzodiazepine receptor ligands[J]. Neurochem Res, 1997,22(4):419-425
doi: 10.1023/A:1027303609517
[32] Kim HC, Choi DY, Jhoo WK, Lee DW, Koo CH, Kim C. Aspalatone, a new antiplatelet agent , attenuates the neurotoxicity induced by kainic acid in the rat[J].Life Sci, 1997, 61(24):PL373-PL381
[33] Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, Hong JS, Yoneda Y, Kim HC . Role of oxidative stress in epileptic seizures[J]. Neurochem Int, 2011,59(2):122-137
doi: 10.1016/j.neuint.2011.03.025
[34] Dal-Pizzol F, Klamt F, Vianna MM , Schrder N, Quevedo J, Benfato MS, Moreira JC, Walz R. Lipid peroxidation in hippocampus early and late after status epilepticus induced by pilocarpine or kainic acid in Wistar rats. Neurosci Lett 2000; 291(3):179-182.
doi: 10.1016/S0304-3940(00)01409-9
[35] Ueda Y, Yokoyama H, Nakajima A, Tokumaru J , Doi T, Mitsuyama Y.Glutamate excess and free radical formation during and following kainic acid-induced status epilepticus[J].Exp Brain Res,2002,147(2):219-226
doi: 10.1007/s00221-002-1224-4
[36] Dringen R . Metabolism and functions of glutathione in brain[J]. Prog Neurobiol, 2000,62(6):649-671
doi: 10.1016/S0301-0082(99)00060-X
[37] Janáky R, Ogita K, Pasqualotto BA, Bains JS, Oja SS, Yoneda Y, Shaw CA . Glutathione and signal transduction in the mammalian CNS[J]. J Neurochem, 1999,73(3):889-902
[38] Aguiar CC, Almeida AB , Araújo PV, de Abreu RN, Chaves EM, do Vale OC, Macêdo DS, Woods DJ, Fonteles MM, Vasconcelos SM.Oxidative stress and epilepsy: literature review[J]. Oxid Med Cell Longev, 2012,2012:795259
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