View More View Less
  • 1 University of Erciyes Department of Biology, Faculty of Science Kayseri Turkey
  • 2 Karadeniz Technical University Department of Physiology, Faculty of Medicine Trabzon Turkey
  • 3 University of Ondokuz Mayis Department of Physiology, Faculty of Medicine 55139 Samsun Turkey
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $752.00

Grape seed extract (GSE) has been known as being neuroprotective due to its antioxidant properties. The aim of the present study was to examine both the effect of GSE on the penicillin-induced epileptiform activity in rat and the role of nitric oxide (NO) pathway in the effect of GSE. GSE, at doses of 50, 100, 200 mg/kg, significantly decreased the mean frequency of epileptiform activity. GSE, at the highest dose (400 mg/kg), did not change either the frequency or amplitude of epileptiform activity. GSE, at a dose of 200 mg/kg, was the most effective in changing the frequency of epileptiform activity. The occurrence of anticonvulsant activity of GSE was significantly delayed in the presence of selective inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (60 mg/kg), which was inhibited by the NO precursor, L-arginine (500 mg/kg). The administration of a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) partially reversed the anticonvulsant activity of GSE. Selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI) and L-arginine showed a similar anticonvulsant activity in the presence of GSE. The electrophysiological evidence of the present study indicates that GSE decreases the mean frequency of penicillin-induced epileptiform activity, suggesting an anticonvulsant role. iNOS/NO pathway could be involved in mediating anticonvulsant effect of GSE on the epileptiform activity.

  • Akagawa M, Shigemitsu T, Suyama K: Production of hydrogen peroxide by polyphenols and polyphenol-rich beverages under quasi-physiological conditions. Biosci. Biotechnol. Biochem. 67, 2632–2640 (2003)

    Suyama K. , 'Production of hydrogen peroxide by polyphenols and polyphenol-rich beverages under quasi-physiological conditions ' (2003 ) 67 Biosci. Biotechnol. Biochem. : 2632 -2640.

    • Search Google Scholar
  • Ariga T: The antioxidative function, preventive action on disease and utilization of proanthocyanidins. Biofactors 21, 197–201 (2004)

    Ariga T. , 'The antioxidative function, preventive action on disease and utilization of proanthocyanidins ' (2004 ) 21 Biofactors : 197 -201.

    • Search Google Scholar
  • Aslan A, Yildirim M, Ayyildiz M, Guven A, Agar E: Interaction of leptin and nitric oxide pathway on penicillin-induced epileptiform activity in rats. Brain Res. 1321, 117–124 (2010)

    Agar E. , 'Interaction of leptin and nitric oxide pathway on penicillin-induced epileptiform activity in rats ' (2010 ) 1321 Brain Res. : 117 -124.

    • Search Google Scholar
  • Ayyildiz M, Yildirim M, Agar E: The involvement of nitric oxide in the anticonvulsant effects of alphatocopherol on penicillin-induced epileptiform activity in rats. Epilepsy Res. 73, 166–172 (2007)

    Agar E. , 'The involvement of nitric oxide in the anticonvulsant effects of alphatocopherol on penicillin-induced epileptiform activity in rats ' (2007 ) 73 Epilepsy Res. : 166 -172.

    • Search Google Scholar
  • Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ: Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res. Commun. Mol. Pathol. Pharmacol. 95, 179–189 (1997)

    Stohs S.J. , 'Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro ' (1997 ) 95 Res. Commun. Mol. Pathol. Pharmacol. : 179 -189.

    • Search Google Scholar
  • Balu M, Sangeetha P, Murali G, Panneerselvam C: Modulatory role of grape seed extract on age-related oxidative DNA damage in central nervous system of rats. Brain Res. Bull. 68, 469–473 (2006)

    Panneerselvam C. , 'Modulatory role of grape seed extract on age-related oxidative DNA damage in central nervous system of rats ' (2006 ) 68 Brain Res. Bull. : 469 -473.

    • Search Google Scholar
  • Bosnak M, Ayyildiz M, Yildirim M, Agar E: The role of nitric oxide in the anticonvulsant effects of pyridoxine on penicillin-induced epileptiform activity in rats. Epilepsy Res. 76, 49–59 (2007)

    Agar E. , 'The role of nitric oxide in the anticonvulsant effects of pyridoxine on penicillin-induced epileptiform activity in rats ' (2007 ) 76 Epilepsy Res. : 49 -59.

    • Search Google Scholar
  • Bredt DS, Glatt CE, Hwang PM, Fotuhi M, Dawson TM, Snyder SH: Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron 7, 615–624 (1991)

    Snyder S.H. , 'Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase ' (1991 ) 7 Neuron : 615 -624.

    • Search Google Scholar
  • Buisson A, Lackhmeche N, Verrecia C, Plotkine M, Bolou RG: Nitric oxide: an endogenous anticonvulsant substance. Neuroreport 4, 444–446 (1993)

    Bolou R.G. , 'Nitric oxide: an endogenous anticonvulsant substance ' (1993 ) 4 Neuroreport : 444 -446.

    • Search Google Scholar
  • Byun JS, Lee SH, Jeon SH, Kwon YS, Lee HJ, Kim SS, Kim YM, Kim MJ, Chun W: Kainic acid-induced neuronal death is attenuated by aminoguanidine but aggravated by L-NAME in mouse hippocampus. Korean J. Physiol. Pharmacol. 13, 265–271 (2009)

    Chun W. , 'Kainic acid-induced neuronal death is attenuated by aminoguanidine but aggravated by L-NAME in mouse hippocampus ' (2009 ) 13 Korean J. Physiol. Pharmacol. : 265 -271.

    • Search Google Scholar
  • Devi PU, Manocha A, Vohora D: Seizures, antiepileptics, antioxidants and oxidative stress: an insight for researchers. Expert. Opin. Pharmacother. 9, 3169–3177 (2008)

    Vohora D. , 'Seizures, antiepileptics, antioxidants and oxidative stress: an insight for researchers ' (2008 ) 9 Expert. Opin. Pharmacother. : 3169 -3177.

    • Search Google Scholar
  • Devi A, Jolitha AB, Ishii N: Grape seed proanthocyanidin extract (GSPE) and antioxidant defense in the brain of adult rats. Med. Sci. Monit. 12, BR124–129 (2006)

    Ishii N. , 'Grape seed proanthocyanidin extract (GSPE) and antioxidant defense in the brain of adult rats ' (2006 ) 12 Med. Sci. Monit. : BR124 -129.

    • Search Google Scholar
  • Edirisinghe I, Burton-Freeman B, Tissa Kappagoda C: Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract. Clin. Sci. (Lond). 114, 331–337 (2008)

    Tissa Kappagoda C. , 'Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract ' (2008 ) 114 Clin. Sci. (Lond). : 331 -337.

    • Search Google Scholar
  • Feng Y, Liu YM, Fratkins JD, LeBlanc MH: Grape seed extract suppresses lipid peroxidation and reduces hypoxic ischemic brain injury in neonatal rats. Brain Res. Bull. 66, 120–127 (2005)

    LeBlanc M.H. , 'Grape seed extract suppresses lipid peroxidation and reduces hypoxic ischemic brain injury in neonatal rats ' (2005 ) 66 Brain Res. Bull. : 120 -127.

    • Search Google Scholar
  • Feng Y, Liu YM, Leblanc MH, Bhatt AJ, Rhodes PG: Grape seed extract given three hours after injury suppresses lipid peroxidation and reduces hypoxic-ischemic brain injury in neonatal rats. Pediatr. Res. 61, 295–300 (2007)

    Rhodes P.G. , 'Grape seed extract given three hours after injury suppresses lipid peroxidation and reduces hypoxic-ischemic brain injury in neonatal rats ' (2007 ) 61 Pediatr. Res. : 295 -300.

    • Search Google Scholar
  • Ferraro G, Montalbano ME, La Grutta V: NO and hippocampal epilepsy: an electrophysiological evidence of a new modulatory system. Epilepsia 38, 190–191 (1997)

    Grutta V. , 'NO and hippocampal epilepsy: an electrophysiological evidence of a new modulatory system ' (1997 ) 38 Epilepsia : 190 -191.

    • Search Google Scholar
  • Frantseva MV, Velazquez JLP, Tsoraklidis G, Mendonca AJ, Adamchik YL, Mills R, Carlen PL, Burnham MW: Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience 97, 431–435 (2000)

    Burnham M.W. , 'Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy ' (2000 ) 97 Neuroscience : 431 -435.

    • Search Google Scholar
  • Garthwaite J: Glutamate, nitric oxide and cell-cell signaling in the nervous system. Trends Neurosci. 14: 60–67 (1991)

    Garthwaite J. , 'Glutamate, nitric oxide and cell-cell signaling in the nervous system ' (1991 ) 14 Trends Neurosci. : 60 -67.

    • Search Google Scholar
  • Homayoun H, Khavandgar S, Dehpour AR: Anticonvulsant effects of cyclosporine A on pentylenetetrazole-induced seizure and kindling: modulation by nitricoxidergic system. Brain Res. 939, 1–10 (2002)

    Dehpour A.R. , 'Anticonvulsant effects of cyclosporine A on pentylenetetrazole-induced seizure and kindling: modulation by nitricoxidergic system ' (2002 ) 939 Brain Res. : 1 -10.

    • Search Google Scholar
  • Hwang IK, Yoo KY, Kim DS, Jeong YK, Kim JD, Shin HK, Lim SS, Yoo ID, Kang TC, Kim DW, Moon WK, Won MH: Neuroprotective effects of grape seed extract on neuronal injury by inhibiting DNA damage in the gerbil hippocampus after transient forebrain ischemia. Life Sci. 75, 1989–2001 (2004)

    Won M.H. , 'Neuroprotective effects of grape seed extract on neuronal injury by inhibiting DNA damage in the gerbil hippocampus after transient forebrain ischemia ' (2004 ) 75 Life Sci. : 1989 -2001.

    • Search Google Scholar
  • Jerrett SA, Jefferson D, Mengel CE: Seizures, H2O2 formation and lipid peroxides in brain during exposure to oxygen under high pressure. Aerosp. Med. 44, 40–44 (1973)

    Mengel C.E. , 'Seizures, H2O2 formation and lipid peroxides in brain during exposure to oxygen under high pressure ' (1973 ) 44 Aerosp. Med. : 40 -44.

    • Search Google Scholar
  • Kozan R, Ayyildiz M, Agar E: The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats. Epilepsia 50, 1760–1767 (2009)

    Agar E. , 'The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats ' (2009 ) 50 Epilepsia : 1760 -1767.

    • Search Google Scholar
  • Laszlo F, Evans SM, Whittle BJ: Aminoguanidine inhibits both constitutive and inducible nitric oxide synthase isoforms in rat intestinal microvasculature in vivo. Eur. J. Pharmacol. 272, 169–175 (1995)

    Whittle B.J. , 'Aminoguanidine inhibits both constitutive and inducible nitric oxide synthase isoforms in rat intestinal microvasculature in vivo ' (1995 ) 272 Eur. J. Pharmacol. : 169 -175.

    • Search Google Scholar
  • Levy SL, Burnham WM, Bishai A, Hwang PA: The anticonvulsant effects of vitamin E: a further evaluation. Can. J. Neurol. Sci. 19, 201–203 (1992)

    Hwang P.A. , 'The anticonvulsant effects of vitamin E: a further evaluation ' (1992 ) 19 Can. J. Neurol. Sci. : 201 -203.

    • Search Google Scholar
  • Morin B, Narbonne JF, Ribera D, Badouard C, Ravanat JL: Effect of dietary fat-soluble vitamins A and E and proanthocyanidin-rich extract from grape seeds on oxidative DNA damage in rats. Food Chem. Toxicol. 46, 787–796 (2008)

    Ravanat J.L. , 'Effect of dietary fat-soluble vitamins A and E and proanthocyanidin-rich extract from grape seeds on oxidative DNA damage in rats ' (2008 ) 46 Food Chem. Toxicol. : 787 -796.

    • Search Google Scholar
  • Mulsch A, Busse R, Mordvintcev PI, Vanin AF, Nielsen EO, Scheel-Kruger J, Olsen SP: Nitric oxide promotes seizure activity in kainate-treated rats. Neuroreport 5, 2325–2328 (1994)

    Olsen S.P. , 'Nitric oxide promotes seizure activity in kainate-treated rats ' (1994 ) 5 Neuroreport : 2325 -2328.

    • Search Google Scholar
  • Oliver CN, Starke-Reed PE, Stadtman ER, Lin GJ, Correy JM, Floyd RA: Oxidative damage to brain proteins, loss of glutamine synthetase activity and production of free radicals during ischemia/reperfusion induced injury to gerbil brain. Proc. Natl Acad. Sci. USA 87, 5144–5147 (1990)

    Floyd R.A. , 'Oxidative damage to brain proteins, loss of glutamine synthetase activity and production of free radicals during ischemia/reperfusion induced injury to gerbil brain ' (1990 ) 87 Proc. Natl Acad. Sci. USA : 5144 -5147.

    • Search Google Scholar
  • Paxinos G, Watson C (1986): The rat brain in stereotaxic coordinates. Academic Press, Sydney

    Watson C. , '', in The rat brain in stereotaxic coordinates , (1986 ) -.

  • Penix LP, Davis W, Subramaniam S: Inhibition of NO synthase increases the severity of kainic acid-induced seizures in mice. Epilepsy Res. 18, 177–184 (1994)

    Subramaniam S. , 'Inhibition of NO synthase increases the severity of kainic acid-induced seizures in mice ' (1994 ) 18 Epilepsy Res. : 177 -184.

    • Search Google Scholar
  • Punathil T, Katiyar SK: Inhibition of non-small cell lung cancer cell migration by grape seed proanthocyanidins is mediated through the inhibition of nitric oxide, guanylate cyclase, and ERK1/2. Mol. Carcinog. 48, 232–242 (2009)

    Katiyar S.K. , 'Inhibition of non-small cell lung cancer cell migration by grape seed proanthocyanidins is mediated through the inhibition of nitric oxide, guanylate cyclase, and ERK1/2 ' (2009 ) 48 Mol. Carcinog. : 232 -242.

    • Search Google Scholar
  • Rehni AK, Singh TG, Kalra R, Singh N: Pharmacological inhibition of inducible nitric oxide synthase attenuates the development of seizures in mice. Nitric Oxide 21, 120–125 (2009)

    Singh N. , 'Pharmacological inhibition of inducible nitric oxide synthase attenuates the development of seizures in mice ' (2009 ) 21 Nitric Oxide : 120 -125.

    • Search Google Scholar
  • Shao ZH, Hsu CW, Chang WT, Waypa GB, Li J, Li D, Li CQ, Anderson T, Qin Y, Schumacker PT, Becker LB, Hoek TL: Cytotoxicity induced by grape seed proanthocyanidins: role of nitric oxide. Cell. Biol. Toxicol. 22, 149–158 (2006)

    Hoek T.L. , 'Cytotoxicity induced by grape seed proanthocyanidins: role of nitric oxide ' (2006 ) 22 Cell. Biol. Toxicol. : 149 -158.

    • Search Google Scholar
  • Shao ZH, Wojcik KR, Dossumbekova A, Hsu C, Mehendale SR, Li CQ, Qin Y, Sharp WW, Chang WT, Hamann KJ, Yuan CS, Hoek TL: Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling. J. Cell. Biochem. 107, 697–705 (2009)

    Hoek T.L. , 'Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling ' (2009 ) 107 J. Cell. Biochem. : 697 -705.

    • Search Google Scholar
  • Shao ZH, Vanden Hoek TL, Xie J, Wojcik K, Chan KC, Li CQ, Hamann K, Qin Y, Schumacker PT, Becker LB, Yuan CS: Grape seed proanthocyanidins induce pro-oxidant toxicity in cardiomyocytes. Cardiovasc. Toxicol. 3, 331–339 (2003)

    Yuan C.S. , 'Grape seed proanthocyanidins induce pro-oxidant toxicity in cardiomyocytes ' (2003 ) 3 Cardiovasc. Toxicol. : 331 -339.

    • Search Google Scholar
  • Smith SE, Man CM, Yip PK, Tang E, Chapman AG, Meldrum BS: Anticonvulsant effects of 7-nitroindazole in rodents with reflex epilepsy may result from L-arginine accumulation or a reduction in nitric oxide or L-citrulline formation. Br. J. Pharmacol. 119, 165–173 (1996)

    Meldrum B.S. , 'Anticonvulsant effects of 7-nitroindazole in rodents with reflex epilepsy may result from L-arginine accumulation or a reduction in nitric oxide or L-citrulline formation ' (1996 ) 119 Br. J. Pharmacol. : 165 -173.

    • Search Google Scholar
  • Tomé AR, Feng D, Freitas RM: The effects of alpha-tocopherol on hippocampal oxidative stress prior to in pilocarpine-induced seizures. Neurochem. Res. 35, 580–587 (2010)

    Freitas R.M. , 'The effects of alpha-tocopherol on hippocampal oxidative stress prior to in pilocarpine-induced seizures ' (2010 ) 35 Neurochem. Res. : 580 -587.

    • Search Google Scholar
  • Tutka P, Barczyński B, Arent K, Mosiewicz J, Mróz T, Wielosz M: Different effects of nitric oxide synthase inhibitors on convulsions induced by nicotine in mice. Pharmacol. Rep. 59, 259–267 (2007)

    Wielosz M. , 'Different effects of nitric oxide synthase inhibitors on convulsions induced by nicotine in mice ' (2007 ) 59 Pharmacol. Rep. : 259 -267.

    • Search Google Scholar
  • Wang Q, Simonyi A, Li W, Sisk BA, Miller RL, Macdonald RS, Lubahn DE, Sun GY, Sun AY: Dietary grape supplement ameliorates cerebral ischemia-induced neuronal death in gerbils. Mol. Nutr. Food Res. 49, 443–451 (2005)

    Sun A.Y. , 'Dietary grape supplement ameliorates cerebral ischemia-induced neuronal death in gerbils ' (2005 ) 49 Mol. Nutr. Food Res. : 443 -451.

    • Search Google Scholar
  • Wang YJ, Thomas P, Zhong JH, Bi FF, Kosaraju S, Pollard A, Fenech M, Zhou XF: Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer’s disease mouse. Neurotox. Res. 15, 3–14 (2009)

    Zhou X.F. , 'Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer’s disease mouse ' (2009 ) 15 Neurotox. Res. : 3 -14.

    • Search Google Scholar
  • Yang GY, Liao J, Li C, Chung J, Yurkow EJ, Ho CT, Yang CS: Effect of black and green tea polyphenols on c-jun phosphorylation and H(2)O(2) production in transformed and non-transformed human bronchial cell lines: possible mechanisms of cell growth inhibition and apoptosis induction. Carcinogenesis 21, 2035–2039 (2000)

    Yang C.S. , 'Effect of black and green tea polyphenols on c-jun phosphorylation and H(2)O(2) production in transformed and non-transformed human bronchial cell lines: possible mechanisms of cell growth inhibition and apoptosis induction ' (2000 ) 21 Carcinogenesis : 2035 -2039.

    • Search Google Scholar
  • Yasuda H, Fuji M, Fujisawa H, Ito H, Suzuki M: Changes in nitric oxide synthesis and epileptic activity in the contralateral hippocampus of rats following intrahippocampal kainate injection. Epilepsia 42, 13–20 (2001)

    Suzuki M. , 'Changes in nitric oxide synthesis and epileptic activity in the contralateral hippocampus of rats following intrahippocampal kainate injection ' (2001 ) 42 Epilepsia : 13 -20.

    • Search Google Scholar
  • Yildirim M, Ayyildiz M, Agar E: Endothelial nitric oxide synthase activity involves in the protective effect of ascorbic acid against penicillin-induced epileptiform activity. Seizure 19, 102–108 (2010)

    Agar E. , 'Endothelial nitric oxide synthase activity involves in the protective effect of ascorbic acid against penicillin-induced epileptiform activity ' (2010 ) 19 Seizure : 102 -108.

    • Search Google Scholar

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Sep 2020 9 0 0
Oct 2020 2 0 0
Nov 2020 1 1 0
Dec 2020 1 0 0
Jan 2021 1 0 0
Feb 2021 0 0 0
Mar 2021 0 0 0