Neurochemical Research

, Volume 38, Issue 1, pp 174–185 | Cite as

Evaluation of the Possible Epileptogenic Activity of Ciprofloxacin: The Role of Nigella sativa on Amino Acids Neurotransmitters

  • Nadia M. S. Arafa
  • Mona Abdel-Rahman
  • Manal F. El-khadragy
  • Rami B. Kassab
Original Paper


The neuroprotective effect of Nigella sativa (NS) on amino acid neurotransmitters alteration in pentylenetetrazole (PTZ) and ciprofloxacin (CFX) treated rats in different brain regions was examined. The oral administration of NS induced an elevation in aspartate and glutamate contents, whereas the levels of GABA and glycine were decreased. Furthermore, the treated groups with PTZ and CFX caused a decrease in aspartate, glutamate and total antioxidant capacity levels, while the concentrations of GABA and glycine were increased after 14 days. Moreover, the pre- and post-treatment with NS in PTZ and CFX treated rats return the levels of these parameters near control values. So, it could be concluded that the treatment with CFX induced imbalance between the excitatory and the inhibitory amino acids which may lead to the initiation of epileptic seizures and the treatment with NS was found to ameliorate these neurological defects which reflect its potent antiepileptic activity.


Epilepsy Nigella sativa Ciprofloxacin PTZ Aspartate Glutamate GABA Glycine 


  1. 1.
    WHO (2001) Epilepsy: aetiology, epidemiology and prognosis. Fact sheet No. 165Google Scholar
  2. 2.
    Urbanska EM, Czuczwar SJ, Kleinrok Z, Turski WA (1998) Excitatory amino acids in epilepsy. Restor Neurol Neurosci 13:25–39PubMedGoogle Scholar
  3. 3.
    Lode H, Borner K, Koeppe P (1998) Pharmacodynamics of fluoroquinolones. Clin Infect Dis 27:33–39PubMedCrossRefGoogle Scholar
  4. 4.
    Petri WA (2011) Sulfonamides, trimethoprim-sulfomethoxazole, quinolones and agents for urinary tract infections. In: Brunton LL (ed) Goodmans and Gilman’s the pharmacological basis of therapeutics, 12th edn. The MaGraw-Hill Companies Inc., New York, pp 1463–1476Google Scholar
  5. 5.
    Marians KJ, Hiasa H (1997) Mechanism of quinolone action. A druginduced structural perturbation of the DNA precedes strand cleavage by topoisomerase IV. J Biol Chem 272:9401–9409PubMedCrossRefGoogle Scholar
  6. 6.
    Drlica K (1999) Mechanism of flouroquinolone action. Curr Opin Microbiol 2:504–508PubMedCrossRefGoogle Scholar
  7. 7.
    Salem ML (2005) Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol 5:1749–1770PubMedCrossRefGoogle Scholar
  8. 8.
    Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar M (2000) Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie 55:379–382PubMedGoogle Scholar
  9. 9.
    Kanter M, Coskun O, Korkmaz A, Oter S (2004) Effects of Nigella sativa on oxidative stress and beta-cell damage in streptozocin-induced diabetic rats. Anat Rec A Discov Mol Cell Evol Biol 279(1):685–691PubMedCrossRefGoogle Scholar
  10. 10.
    Kanter M, Coskun O, Budancamanak M (2005) Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol 11:6684–6688PubMedGoogle Scholar
  11. 11.
    Kanter M, Demir H, Karakaya C, Ozbek H (2005) Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World J Gastroenterol 11:6662–6666PubMedGoogle Scholar
  12. 12.
    Kanter M, Coskun O, Uysal H (2006) The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol 80:217–224PubMedCrossRefGoogle Scholar
  13. 13.
    Kanter M, Coskun O, Kalayci M, Buyukbas S, Cagavi F (2006) Neuroprotective effects of Nigella sativa on experimental spinal cord injury in rats. Hum Exp Toxicol 25:127–133PubMedCrossRefGoogle Scholar
  14. 14.
    Kanter M (2008) Nigella sativa and derived thymoquinone prevents hippocampal neurodegen- eration after chronic toluene exposure in rats. Neurochem Res 33:579–588PubMedCrossRefGoogle Scholar
  15. 15.
    Quintans-Júnior LJ, Silva DA, Siqueira JS, Araújo AAS, Guimarães AG, Araújo RAN, Araújo DAM, Souza MFV, Gutierrez SJC, Barbosa-Filho JM, Almeida RN (2009) Anticonvulsant property of N-salicyloyltryptamine: evidence of enhance of central GABAergic neurotransmission. J Epilepsy Clin Neurophysiol 15(4):165–168CrossRefGoogle Scholar
  16. 16.
    Gurbay A, Hincal F (2004) Ciprofloxacin-induced glutathione redox status alterations in rat tissues. Drug Chem Toxicol 27(3):233–242PubMedCrossRefGoogle Scholar
  17. 17.
    Chen L, Feng P, Wang J, Liu L, Zhou D (2009) Intravenous sodium valproate in mainland China for the treatment of diazepam refractory convulsive status epilepticus. J Clin Neurosci 16:524–526PubMedCrossRefGoogle Scholar
  18. 18.
    Glowinski LJ, Iversen LL (1966) Regional studies of catecholamines in the rat brain. I. Disposition of Ha-noradrenaline, Ha-dopamine and Ha-dopa in various regions of the brain. J Neurochem 13:655–669PubMedCrossRefGoogle Scholar
  19. 19.
    Heinrikson RL, Meredith SC (1984) Amino acid analysis by reverse-phase high-performance liquid chromatography: precolumn derivatization with phenylisothiocyanate. Anal Biochem 136(1):65–74PubMedCrossRefGoogle Scholar
  20. 20.
    Koracevic D, Koracivic G, Djordjevic V, Andregevic S, Costic V (2001) Method for measurement of antioxidant activity in human fluids. J Clin Pathol 54(5):356–361PubMedCrossRefGoogle Scholar
  21. 21.
    Duncan DB (1955) Multiple F-test. Biometrics 11:1–42CrossRefGoogle Scholar
  22. 22.
    Mori N, Wada JA (1987) Bidirectional transfer between kindling induced by excitatory amino acids and electrical stimulation. Brain Res 425:45–48PubMedCrossRefGoogle Scholar
  23. 23.
    Sherwin A, Robitaille Y, Quesney F, Olivier A, Villemure J, Leblanc R, Feindel W, Andermann E, Gotman J, Andermann F, Ethier R, Kish S (1988) Excitatory amino acids are elevated in human epileptic cerebral cortex. Neurology 38(6):920–923PubMedCrossRefGoogle Scholar
  24. 24.
    Croucher MJ, Bradford HJ (1989) Kindling of limbic seizures by repeated microinjections of excitatory amino acids into the rat amygdala. Brain Res 501:58–65PubMedCrossRefGoogle Scholar
  25. 25.
    Bozzi Y, Vallone D, Borrelli E (2000) Neuroprotective role of dopamine against hippocampal cell death. J Neurosci 20(22):8643–8649PubMedGoogle Scholar
  26. 26.
    Marini AM, Jiang X, Wu X, Pan H, Guo Z, Mattson MP, Blondeau N, Novelli A, Lipsky RH (2007) Preconditioning and neurotrophins: a model for brain adaptation to seizures, ischemia and other stressful stimuli. Amino Acids 32:299–304PubMedCrossRefGoogle Scholar
  27. 27.
    Aroniadou-Anderjaskaa V, Fritsch B, Felicia Qashub F, Maria FM, Bragaa MFM (2008) Pathology and pathophysiology of the amygdala in epileptogenesis and epilepsy. Epilepsy Res 78:102–116CrossRefGoogle Scholar
  28. 28.
    Ito M, Tsuda H, Oguro K (1990) GABA-gated chloride ion influx in brains of epileptic E1 mice. Neurochem Res 15:933–936PubMedCrossRefGoogle Scholar
  29. 29.
    Treiman DM (2001) GABAergic mechanisms in epilepsy. Epilepsia 42(3):8–12PubMedCrossRefGoogle Scholar
  30. 30.
    Gundersen RY, Vaagenes P, Breivik T, Fonnum F, Opstad PK (2005) Glycine-an important neurotransmitter and cytoprotective agent. Acta Anaesthesiol Scand 49(8):1108–1116PubMedCrossRefGoogle Scholar
  31. 31.
    Tonshin AA, Lobysheva NV, Yaguzhinsky LS, Bezgina EN, Moshkov DA, Nartsissov YR (2007) Effect of the inhibitory neurotransmitter glycine on slow destructive processes in brain cortex slices under anoxic conditions. Biochemistry (Mosc) 72(5):509–517CrossRefGoogle Scholar
  32. 32.
    Takazawa A, Murashima YL, Minatogawa Y, Kojima T, Tanaka K, Yamauchi T (1995) In vivo microdialysis monitoring for extracellular glutamate and GABA in the ventral hippocampus of the awake rat during kainate-induced seizures. Psychiatry Clin Neurosci 49(3):275–277CrossRefGoogle Scholar
  33. 33.
    Henry TR (1996) Functional neuroimaging with positron emission tomography. Epilepsia 37:1141–1154PubMedCrossRefGoogle Scholar
  34. 34.
    Jefferys JGR (1993) The pathophysiology of epilepsies. In: Laidlaw J, Richens A, Chadwick D (eds) A textbook of epilepsy. Churchill Livingstone, London, pp 241–276Google Scholar
  35. 35.
    Willoughby JO, Mackenzie L, Medvedev A, Hiscock JJ (1995) Distribution of Fospositive neurons in cortical and subcortical structures after picrotoxin-induced convulsions varies with seizure type. Brain Res 683:73–87PubMedCrossRefGoogle Scholar
  36. 36.
    Corda MC, Orlandi M, Lecca D, Glorgi O (1992) Decrease in GABAergic function induced by pentylenetetrazol kindling in rats. Antagonism by MK-801. J Pharmacol Exp Ther 262:792–800PubMedGoogle Scholar
  37. 37.
    Rocha L, Briones M, Ackermann RF, Anton B, Maidment NT, Evans CJ, Engel J (1996) Pentylenetetrazol-induced kindling: early involvement of excitatory and inhibitory systems. Epilepsy Res 26:105–113PubMedCrossRefGoogle Scholar
  38. 38.
    Macdonald RL, Barker JL (1979) Enhancement of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of anticonvulsant action. Brain Res 167:323–336PubMedCrossRefGoogle Scholar
  39. 39.
    Ha JH, Lee DU, Lee JT, Kim JS, Yong CS, Kim JA (2000) 4-Hydroxybenzaldehyde from Gastrodia elata as active in the antioxidation and GABAergic neuromodulation of the rat brain. J Ethnopharmacol 73:329–333PubMedCrossRefGoogle Scholar
  40. 40.
    Wong RK, Watkins DJ (1982) Cellular factors influencing GABA response in hippocampal pyramidal cells. J Neurophysiol 48:938–951PubMedGoogle Scholar
  41. 41.
    Van Gelder NM, Sherwin AL, Sacks C, Anderman F (1975) Biochemical observations following administration of taurine to patients with epilepsy. Brain Res 94(2):297–306PubMedCrossRefGoogle Scholar
  42. 42.
    Schroder H, Becker A, Lossner B (1993) Glutamate binding to brain membrane is increased in pentylenetetrazol-kindled rats. J Neurochem 60:1007–1011PubMedCrossRefGoogle Scholar
  43. 43.
    Schroder H, Becker A (1996) The role of glutamate receptors in pentylenetetrazole kindling of rats: a neurochemical study. Neuropharmacology 35:A28CrossRefGoogle Scholar
  44. 44.
    During MJ, Spencer DD (1993) Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 341:1607–1610PubMedCrossRefGoogle Scholar
  45. 45.
    Rowley HL, Martin KF, Marsden CA (1995) Decreased GABA release following tonic-clonic seizures is associated with an increase in extracellular glutamate in rat hippocampus in vivo. Neuroscience 68:415–422PubMedCrossRefGoogle Scholar
  46. 46.
    Schroder H, Becker A, Hollt V (1998) Sensitivity and density of glutamate receptor subtypes in the hippocampal formation are altered in pentylenetetrazol-kindled rats. Exp Brain Res 120:527–530CrossRefGoogle Scholar
  47. 47.
    Li ZP, Zhang XY, Lu X, Zhong MK, Ji YH (2004) Dynamic release of amino acid transmitters induced by valproate in PTZ kindled epileptic rat hippocampus. Neurochem Int 44:264–270CrossRefGoogle Scholar
  48. 48.
    Sherwin AL (1999) Neuroactive amino acids in focally epileptic human brain: a review. Neurochem Res 24(11):1387–1395PubMedCrossRefGoogle Scholar
  49. 49.
    Unseld E, Ziegler G, Gemeinhardt A, Janssen U, Klotz U (1990) Possible interaction of fluoroquinolones with the benzodiazepine-GABAAreceptor complex. Br J Clin Pharmacol 30:63–70PubMedCrossRefGoogle Scholar
  50. 50.
    Akahane K, Tsutomi Y, Kimura Y, Kitano Y (1994) Levofloxacin, an optical isomer of ofloxacin, has attenuated epileptogenic activity in mice and inhibitory potency in GABA receptor binding. Chemother 40:412–417CrossRefGoogle Scholar
  51. 51.
    Imanishi T, Akahane K, Akaike N (1995) Attenuated inhibition by levofloxacin, l-isomer of ofloxacin, on GABA response in the dissociated rat hippocampal neurons. Neurosci Lett 193:81–84PubMedCrossRefGoogle Scholar
  52. 52.
    Halliwell RF, Davery PG, Lambert JJ (1993) Antagonism of GABAA receptors by 4-quinolones. J Antimicrob Chemother 31:457–462PubMedCrossRefGoogle Scholar
  53. 53.
    Akaike N, Shirasaki T, Yakushiji T (1991) Quinolones and fenbufen interact with GABAA receptors in dissociated hippocampal cells of the rat. J Neurophysiol 66:497–504PubMedGoogle Scholar
  54. 54.
    Tsuji A, Sato H, Kume Y, Tamai I, Okezaki E, Nagata O, Kato H (1988) Inhibitory effects of quinolone antibacterial agents on gamma-aminobutyric acid binding to receptor sites in rat brain membranes. Antimicrob Agents Chemother 32:190–194PubMedCrossRefGoogle Scholar
  55. 55.
    De Sarro A, Trimarchi GR, Ammendola D, De Sarro G (1992) Repeated treatment with quinolones potentiates the seizures induced by aminophylline in genetically epilepsy-prone rats. Gen Pharmacol 23:853–959PubMedCrossRefGoogle Scholar
  56. 56.
    Akahane K, Kato M, Takayama S (1993) Involvement of inhibitory and excitatory neurotransmitters in levofloxacin and ciprofloxacin-induced convulsions in mice. Antimicrob Agents Chemother 37:1764–1770PubMedCrossRefGoogle Scholar
  57. 57.
    Dimpfel W, Dalhoff A, Von Keutz E (1996) In vitro modulation of hippocampal pyramidal cell response by quinolones: effects of HA966 and γ-hydroxybutyric acid. Antimicrob Agents Chemother 40:2573–2576PubMedGoogle Scholar
  58. 58.
    Williams PD, Helton DR (1991) The proconvulsive activity of quinolone antibiotics in an animal model. Toxicol Lett 58:23–28PubMedCrossRefGoogle Scholar
  59. 59.
    Kushner JM, Peckman HJ, Snyder CR (2001) Seizures associated with fluoroquinolones. Ann Pharmacother 35(10):1194–1198PubMedCrossRefGoogle Scholar
  60. 60.
    Kisa C, Yildirim SG, Aydemir C, Cebeci S, Goka E (2005) Prolonged electroconvulsive therapy seizure in a patient taking ciprofloxacin. J ECT 21(1):43–44PubMedCrossRefGoogle Scholar
  61. 61.
    Tattevin P, Messiaen T, Pras V, Ronco P, Biour M (1998) Confusion and general seizures following ciprofloxacin administration. Nephrol Dial Transplant 13(10):2712–2713PubMedCrossRefGoogle Scholar
  62. 62.
    Darwish T (2008) Ciprofloxacin-induced seizures in a healthy patient. NZ Med J 121(1277):104–105Google Scholar
  63. 63.
    Grimm O, Alm B, Fur Seelische Z (2007) A case of ciprofloxacin-induced acute polymorphic psychosis with a distinct deficit in executive functions. Psychosomatics 48(3):269PubMedCrossRefGoogle Scholar
  64. 64.
    De Sarro G, Nava F, Calapai G, De Sarro A (1997) Effects of some excitatory amino acid antagonists and drugs enhancing γ-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice. Antimicrob Agents Chemother 41:427–434PubMedGoogle Scholar
  65. 65.
    Rawi SM, Arafa NMS, El-Hazmi MM (2011) Evaluation of the effects of ciprofloxcin or gatifloxacin on neurotransmitters levels in rat cortex and hippocampus. Afr J Pharm Pharmacol 5(8):993–1005. doi: 10.5897/AJPP10.223 Google Scholar
  66. 66.
    Schmuck G, Schurmann A, Schluter G (1998) Determination of the excitatory potencies of fluoroquinolones in the central nervous system by an in vitro model. Antimicrob Agents Chemother 42(7):1831–1836PubMedGoogle Scholar
  67. 67.
    Nozaki M, Takeda N, Tanba M, Turumi S, Fujimura H (1990) Mechanisms of convulsions induced by simultaneous administration of newquinolones and anti-inflammatory agents. Folia Pharmacol Jpn 95:33Google Scholar
  68. 68.
    Murayama S, Suzuki T, Hara Y, Tamagawa M, Kakizaki K (1987) Unusual central action of new quinolone group of antimicrobials. Jpn J Pharmacol 43:60Google Scholar
  69. 69.
    Raza M, El-hadiyah TM, Al-shabanah OA (2006) Nigella sativa seed constituents and anxiety relief in experimental models. J Herbs Spices Med Plants 12:153–164CrossRefGoogle Scholar
  70. 70.
    Gilhotra N, Dhingra D (2011) Thymoquinone produced antianxiety-like effects in mice through modulation of GABA and NO levels. Pharmacol Rep 63:660–669PubMedGoogle Scholar
  71. 71.
    Abdel-Fattah AFM, Matsumoto K, Watanabe H (2000) Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol 400:89–97PubMedCrossRefGoogle Scholar
  72. 72.
    Hosseinzadeh H, Parvardeh S, Nassiri-asl M, Mansouri M (2005) Intra cerebroventricular administration of thymoquinone the major constituent of Nigella sativa seeds suppresses epileptic seizures in rat. Med Sci Monit 11(4):BR106–BR110PubMedGoogle Scholar
  73. 73.
    Werz RL, Macdonald MA (1984) Dynorphin reduces voltage- dependent calcium conductance of mouse dorsal root ganglion neurons. Neuropeptides 5:253–256PubMedCrossRefGoogle Scholar
  74. 74.
    Werz RL, Macdonald MA (1985) Dynorphin and neoendorphin peptides decrease dorsal root ganglion neuron calcium- dependent action potential duration. J Pharmacol Exp Ther 234:49–56PubMedGoogle Scholar
  75. 75.
    Hosseinzadeh H, Parvardeh S (2004) Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine 11(1):56–64PubMedCrossRefGoogle Scholar
  76. 76.
    El-Naggar TB, Gómez-Serranillos MP, Palomino OM, Arce C, Carretero ME (2010) Nigella sativa L. seed extract modulates the neurotransmitter amino acids release in cultured neurons in vitro. J Biomed Biotech 1–8. doi: 10.1155/2010/398312
  77. 77.
    Al-Naggar TB, Gomez-Serranillos MP, Carretero ME, Villar AM (2003) Neuropharmacological activity of Nigella sativa L. extracts. J Ethnopharmacol 88(1):63–68PubMedCrossRefGoogle Scholar
  78. 78.
    Boskabady MH, Shirmohammadi B (2002) Effect of Nigella sativa on isolated guinea pig trachea. Arch Ir Med 5(2):103–107Google Scholar
  79. 79.
    Boskabady MH, Shirmohammadi B, Jandaghi P, Kiani S (2004) Possible mechanism(s) for relaxant effect of aqueous and macerated extracts from Nigella sativa on tracheal chains of guinea pig. BMC Pharmacol. doi: 10.1186/1471-2210-4:3 PubMedGoogle Scholar
  80. 80.
    Boskabady MH, Shafei MN, Parsaee H (2005) Effects of aqueous and macerated extracts from Nigella sativa on guinea pig isolated heart activity. Pharmazie 60(12):943–948PubMedGoogle Scholar
  81. 81.
    Patel M (2004) Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures. Free Radic Biol Med 37:1951–1962PubMedCrossRefGoogle Scholar
  82. 82.
    Shank RP, Doose DR, Streeter AJ, Bialer M (2005) Plasma and whole blood pharmacokinetics of topiramate: the role of carbonic anhydrase. Epilepsy Res 63:103–112PubMedCrossRefGoogle Scholar
  83. 83.
    Naziroglu M, Kutluhan S, Yılmaz M (2008) Selenium and Topiramate modulates oxidative stress and Ca+2-ATPase, EEG records in pentylentetrazol-induced brain seizures in rats. J Membr Biol 225:39–49PubMedCrossRefGoogle Scholar
  84. 84.
    Bruce AJ, Baudry M (1995) Oxygen free radicals in rat limbic structures after kainate-induced seizures. Free Rad Biol Med 18:993–1002PubMedCrossRefGoogle Scholar
  85. 85.
    Rauca C, Zerbe R, Jantze H (1999) Formation of free hydroxyl radicals after pentylenetetrazol induced seizure and kindling. Brain Res 847:347–351PubMedCrossRefGoogle Scholar
  86. 86.
    Erakovic V, Zupan G, Varljen J, Laginja J, Simonic A (2001) Altered activities of rat brain metabolic enzymes caused by pentylenetetrazol kindling and pentylenetetrazol-induced seizures. Epilepsy Res 43:165–173PubMedCrossRefGoogle Scholar
  87. 87.
    Patsoukis N, Zervoudakis G, Georgiou CD, Panagopoulos NT (2005) Thiol redox state and lipid and protein oxidation in the mouse striatum after pentylenetetrazole-induced epileptic seizure. Epilepsia 46(8):1205–1211PubMedCrossRefGoogle Scholar
  88. 88.
    Sood N, Kumar Sahai AK, Medhi B, Chakrabarti A (2008) Dose-finding study with nicotine as a proconvulsant agent in PTZ-induced seizure model in mice. J Biomed Sci 15:755–765PubMedCrossRefGoogle Scholar
  89. 89.
    Halliwell B, Gutteridge JM (1990) Role of free radicals and catalytic metal ions in human disease: An overview. Meth Enzymol 186:1–85PubMedCrossRefGoogle Scholar
  90. 90.
    Sudha K, Rao AV, Rao A (2001) Oxidative stress and antioxidants in epilepsy. Clinica Chemica Acta 303(1–2):19–24CrossRefGoogle Scholar
  91. 91.
    Gurbay A, Gonthier B, Daveloose D, Favier A, Hincal F (2001) Microsomal metabolism of ciprofloxacin generates free radicals. Free Radic Biol Med 30(10):1118–1121PubMedCrossRefGoogle Scholar
  92. 92.
    Becerra MC, Albesa I (2002) Oxidative stress induced by ciprofloxacin in Staphylococcus aureus. Biochem Biophys Res Commun 297:1003–1007PubMedCrossRefGoogle Scholar
  93. 93.
    Albesa I, Becerra MC, Battan PC, Paez PL (2004) Oxidative stress involved in the antibacterial action of different antibiotics. Biochem Biophys Res Commun 317:605–609PubMedCrossRefGoogle Scholar
  94. 94.
    Akhondian J, Parsa A, Rakhshande H (2007) The effect of Nigella sativa L. (black cumin seed) on intractable pediatric seizures. Med Sci Monit 13(12):CR555–CR559PubMedGoogle Scholar
  95. 95.
    Ilhan A, Gurel A, Armutcu F, Kamisli S, Iraz M (2005) Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazol-induced kindling in mice. Neuropharmacology 49:456–464PubMedCrossRefGoogle Scholar
  96. 96.
    Aboul Ezz HS, Khadrawy YA, Noor NA (2011) The neuroprotective effect of curcumin and Nigella sativa oil against oxidative stress in the pilocarpine model of epilepsy: a comparison with valproate. Neurochem Res 36(11):2195–2204CrossRefGoogle Scholar
  97. 97.
    Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T (2007) Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemiareperfusion injury in rat hippocampus. Phytomedicine 14:621–627PubMedCrossRefGoogle Scholar
  98. 98.
    El-Abhar HS, Abdallah M, Saleh S (2003) Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia-reperfusion in rats. J Ethnopharmacol 84:251–258PubMedCrossRefGoogle Scholar
  99. 99.
    Kanter M (2008) Effects of Nigella sativa and its major constituent, thymoquinone on sciatic nerves in experimental diabetic neuropathy. Neurochem Res 33:87–96PubMedCrossRefGoogle Scholar
  100. 100.
    El-Tahir KE, Ashour MM, Al-Harbi MM (1993) The cardiovascular actions of the volatile oil of the black seeds (Nigella sativa) in rats: elucidation of the mechanism of action. Gen Pharmacol 24:1123–1129PubMedCrossRefGoogle Scholar
  101. 101.
    Houghton PI, Zarka R, De las Heras B, Hoult RS (1995) Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med 61:33–36PubMedCrossRefGoogle Scholar
  102. 102.
    Medenica R, Janssens J, Tarasenko A (1997) Anti-angiogenic activity of Nigella sativa plant extract in cancer therapy. Proc Ann Meet Am Assoc Cancer Res 38:1377Google Scholar
  103. 103.
    Badary OA, Abdel-Naim AB, Abdel-Wahab MH, Hamada FM (2000) The influence of thymoquinone on doxorubicininduced hyperlipidemic nephropathy in rats. Toxicol 143:219–226CrossRefGoogle Scholar
  104. 104.
    Al-Ghamdi MS (2001) The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 76:45–48PubMedCrossRefGoogle Scholar
  105. 105.
    Akahane K, Sekiguchi M, Une T, Osada Y (1989) Structure-epileptogenicity relationship of quinolones with special reference to their interaction with γ-aminobutyric acid receptor sites. Antimicrob Agents Chemother 33:1704–1708PubMedCrossRefGoogle Scholar
  106. 106.
    Mohler H (1992) GABAergic synaptic transmission. Regulation by drugs. Arzneim-Forsch 42:211–214Google Scholar
  107. 107.
    De Sarro G, Nava F, Calapai G, De Sarro A (1997) Effects of some excitatory amino acid antagonists and drugs enhancing g-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice. Antimicrob Agents Chemother 41:427–434PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Nadia M. S. Arafa
    • 1
    • 2
  • Mona Abdel-Rahman
    • 3
  • Manal F. El-khadragy
    • 3
  • Rami B. Kassab
    • 3
  1. 1.Biology DepartmentJazan UniversityJazanSaudi Arabia
  2. 2.Department of PhysiologyNational Organization for Drug Control and ResearchGizaEgypt
  3. 3.Zoology and Entomology Department, Faculty of ScienceHelwan UniversityAin Helwan, CairoEgypt

Personalised recommendations