Year 2020, Volume 79 , Issue 2, Pages 124 - 131 2020-12-25

Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats

Savaş USTUNOVA [1] , İsmail MERAL [2] , Abdurrahim KOÇYİĞİT [3] , Aysu KILIC [4] , Oyku ZEYBEK [5] , Mehmet ÜYÜKLÜ [6] , Sedat MEYDAN [7]


Objective: This study was designed for investigating the effectiveness of the Nigella sativa (N. sativa) extract on apoptosis in cerebrum and hippocampus and also plasma oxidative stress, in pentylenetetrazol (PTZ)-induced kindling rats.
Materials and Methods: The kindling model was induced by subconvulsive doses (35 mg/kg i.p.) of intraperitoneal PTZ injections in N. sativa treated and non-treated PTZ groups (PTZ and PTZ + NS). The PTZ + NS group were also treated with an extract of N. sativa (10 mg/kg) 2 h before each PTZ injection. The total oxidant and antioxidant status, oxidative stress index, paraoxonase, arylesterase, catalase (CAT) and total thiol levels were analyzed in plasma. Brain derived neurotrophic factor (BDNF), cyclin-B1 and B-cell lymphoma 2 (Bcl-2) expressions were investigated in the cerebrum and hippocampus.
Results: PTZ decreased the oxidative stress by increasing the activities of CAT, arylesterase, and paraoxonase. N. sativa decreased activities of arylesterase, paraoxonase, while increasing the CAT. It also brought the decreased BDNF and Bcl-2 expression levels to their normal levels in the cerebrum but not in the hippocampus.
Conclusion: N. sativa treatment improved the PTZ induced-impairments in BDNF and Bcl-2 expressions, resulting in a neuronal apoptosis in the cerebrum, without affecting blood oxidative stress.
Apoptosis, Epilepsy, Cerebrum, Hippocampus, N. sativa, Oxidative stress
  • 1. Stafstrom CE, Carmant L. Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harbor Perspect Med 2015;5(6):a022426.
  • 2. Anderson J, Moor C-C. Anti-epileptic drugs: a guide for the non-neurologist. Clin Med (Lond) 2010;10(1):54-8.
  • 3. Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Asian Pac J Trop Biomed 2013;3(5):337-52.
  • 4. Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri M-T. Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. Med Sci Monit 2005;11(4):BR106-BR10.
  • 5. Ilhan A, Gurel A, Armutcu F, Kamisli S, Iraz M. Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazol-induced kindling in mice. Neuropharmacology 2005;49(4):456-64.
  • 6. Dhir A. Pentylenetetrazol (PTZ) kindling model of epilepsy. Curr Protoc Neurosci 2012;58(1):9.37. 1-9.. 12.
  • 7. Radad K, Rausch W-D, Gille G. Rotenone induces cell death in primary dopaminergic culture by increasing ROS production and inhibiting mitochondrial respiration. Neurochem Int 2006;49(4):379-86.
  • 8. Chaudière J, Ferrari-Iliou R. Intracellular antioxidants: from chemical to biochemical mechanisms. Food Chem Toxicol 1999;37(9-10):949-62.
  • 9. Haley RW, Billecke S, La Du BN. Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. Toxicol Appl Pharmacol 1999;157(3):227-33.
  • 10. Hernández AF, Gil F, Lacasaña M, Rodríguez-Barranco M, Gómez-Martin A, Lozano D, et al. Modulation of the endogenous antioxidants paraoxonase-1 and urate by pesticide exposure and genetic variants of xenobiotic-metabolizing enzymes. Food Chem Toxicol 2013;61:164-70.
  • 11. Hobbenaghi R, Javanbakht J, Sadeghzadeh S, Kheradmand D, Abdi F, Jaberi M, et al. Neuroprotective effects of Nigella sativa extract on cell death in hippocampal neurons following experimental global cerebral ischemia-reperfusion injury in rats. J Neurol Sci 2014;337(1-2):74-9.
  • 12. Lucini C, D’Angelo L, Cacialli P, Palladino A, de Girolamo P. BDNF, brain, and regeneration: Insights from zebrafish. Int J Mol Sci 2018;19(10):3155.
  • 13. Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 2012;64(2):238-58.
  • 14. Wolgemuth DJ, Manterola M, Vasileva A. Role of cyclins in controlling progression of mammalian spermatogenesis. Int J Dev Biol 2013;57:159.
  • 15. Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytotherapy Research: An international journal devoted to pharmacological and toxicological evaluation of natural product derivatives. Phytother Res 2003;17(4):299-305.
  • 16. Eraković V, Župan G, Varljen J, Laginja J, Simonić A. Altered activities of rat brain metabolic enzymes caused by pentylenetetrazol kindling and pentylenetetrazol—induced seizures. Epilepsy Res 2001;43(2):165-73.
  • 17. Eckerson HW, Wyte CM, La Du B. The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet 1983;35(6):1126.
  • 18. Haagen L, Brock A. A new automated method for phenotyping arylesterase (EC 3.1. 1.2) based upon inhibition of enzymatic hydrolysis of 4-nitrophenyl acetate by phenyl acetate. Eur J Clin Chem Clin Biochem 1992;30(7):391-6.
  • 19. Kruger NJ. The Bradford method for protein quantitation. Methods Mol Biol 1994; (32):9-15
  • 20. Meral I, Esrefoglu M, Dar K, Ustunova S, Aydin M, Demirtas M, et al. Effects of Nigella sativa on apoptosis and GABAA receptor density in cerebral cortical and hippocampal neurons in pentylenetetrazol induced kindling in rats. Biotech Histochem 2016;91(8):493-500.
  • 21. Pearson-Smith J, Patel M. Metabolic dysfunction and oxidative stress in epilepsy. Int J Mol Sci 2017;18(11):2365.
  • 22. Shi Y, Miao W, Teng J, Zhang L. Ginsenoside Rb1 protects the brain from damage induced by epileptic seizure via Nrf2/ARE signaling. Cell Physiol Biochem 2018;45(1):212-25.
  • 23. Zhu X, Dong J, Han B, Huang R, Zhang A, Xia Z, et al. Neuronal nitric oxide synthase contributes to PTZ kindling epilepsy-induced hippocampal endoplasmic reticulum stress and oxidative damage. Front Cell Neurosci 2017;11:377.
  • 24. Calabrese EJ. Overcompensation stimulation: a mechanism for hormetic effects. Crit Rev Toxicol 2001;31(4-5):425-70.
  • 25. Ungvari Z, Parrado-Fernandez C, Csiszar A, de Cabo R. Mechanisms underlying caloric restriction and lifespan regulation: implications for vascular aging. Circ Res 2008;102(5):519-28.
  • 26. Calabrese EJ, Mattson MP. How does hormesis impact biology, toxicology, and medicine? NPJ Aging Mech Dis 2017;3(1):13.
  • 27. Calabrese EJ, Baldwin LA. Hormesis: a generalizable and unifying hypothesis. Crit Rev Toxicol 2001;31(4-5):353-424.
  • 28. Magesh S, Chen Y, Hu L. Small Molecule Modulators of K eap1‐N rf2‐ARE Pathway as Potential Preventive and Therapeutic Agents. Med Res Rev 2012;32(4):687-726.
  • 29. Ungvari Z, Bagi Z, Feher A, Recchia FA, Sonntag WE, Pearson K, et al. Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol 2010;299(1):H18-H24.
  • 30. Giudice A, Arra C, Turco MC. Review of molecular mechanisms involved in the activation of the Nrf2-ARE signaling pathway by chemopreventive agents. In: Transcription factors. Methods Mol Biol 2010; (634) 37-74.
  • 31. Kamble SM, Goyal SN, Patil CR. Multifunctional pentacyclic triterpenoids as adjuvants in cancer chemotherapy: a review. RSC Advances. 2014;4(63):33370-82.
  • 32. Hamdan AM, Al-Gayyar MM, Shams ME, Alshaman US, Prabahar K, Bagalagel A, et al. Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives. Sci Rep 2019;9(1):7026.
  • 33. Murphy MP. Antioxidants as therapies: can we improve on nature? Free Radic Biol Med 2014;66:20-3.
  • 34. Gaetani GF, Galiano S, Canepa L, Ferraris AM, Kirkman HN. Catalase and glutathione peroxidase are equally active in detoxification of hydrogen peroxide in human erythrocytes. Blood. 1989;73(1):334-9.
  • 35. Alam MF, Khan G, Safhi MM, Alshahrani S, Siddiqui R, Sivagurunathan Moni S, et al. Thymoquinone ameliorates doxorubicin-induced cardiotoxicity in swiss albino mice by modulating oxidative damage and cellular inflammation. Cardiol Res Pract 2018; 1483041 (6 pages).
  • 36. Asgharzadeh F, Bargi R, Beheshti F, Hosseini M, Farzadnia M, Khazaei M. Thymoquinone Prevents Myocardial and Perivascular Fibrosis Induced by Chronic Lipopolysaccharide Exposure in Male Rats:-Thymoquinone and Cardiac Fibrosis. J Pharmacopuncture 2018;21(4):284.
  • 37. Horch HW, Katz LC. BDNF release from single cells elicits local dendritic growth in nearby neurons. Nat Neurosci 2002;5(11):1177.
  • 38. Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci 2015;11(6):1164.
  • 39. Altar CA, Whitehead RE, Chen R, Wörtwein G, Madsen TM. Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain. Biol Psychiatry 2003;54(7):703-9.
  • 40. Falcicchia C, Paolone G, Emerich DF, Lovisari F, Bell WJ, Fradet T, et al. Seizure-suppressant and neuroprotective effects of encapsulated BDNF-producing cells in a rat model of temporal lobe epilepsy. Mol Ther Methods Clin Dev 2018;9:211-24.
  • 41. Porcher C, Medina I, Gaiarsa J-L. Mechanism of BDNF modulation in GABAergic synaptic transmission in healthy and disease brains. Front Cell Neurosci 2018;12:273.
  • 42. Unsain N, Nunez N, Anastasía A, Mascó D. Status epilepticus induces a TrkB to p75 neurotrophin receptor switch and increases brain-derived neurotrophic factor interaction with p75 neurotrophin receptor: an initial event in neuronal injury induction. Neuroscience. 2008;154(3):978-93.
  • 43. Volosin M, Trotter C, Cragnolini A, Kenchappa RS, Light M, Hempstead BL, et al. Induction of proneurotrophins and activation of p75NTR-mediated apoptosis via neurotrophin receptor-interacting factor in hippocampal neurons after seizures. J neurosci 2008;28(39):9870-9.
  • 44. Hong Z, Li W, Qu B, Zou X, Chen J, Sander J, et al. Serum brain‐derived neurotrophic factor levels in epilepsy. Eur J Neurol 2014;21(1):57-64.
  • 45. Chen S-F, Jou S-B, Chen NC, Chuang H-Y, Huang C-R, Tsai M-H, et al. Serum Levels of Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor 1 Are Associated With Autonomic Dysfunction and Impaired Cerebral Autoregulation in Patients With Epilepsy. Front Neurol 2018;9:969.
  • 46. Cosulich SC, Savory PJ, Clarke PR. Bcl-2 regulates amplification of caspase activation by cytochrome c. Curr Biol 1999;9(3):147-50.
  • 47. O'Brien MA, Kirby R. Apoptosis: A review of pro‐apoptotic and anti‐apoptotic pathways and dysregulation in disease. J Vet Emerg Crit Car 2008;18(6):572-85.
  • 48. Hosseini SM, Taghiabadi E, Abnous K, Hariri AT, Pourbakhsh H, Hosseinzadeh H. Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats. Iran J Basic Med Sci 2017;20(8):927.
  • 49. Ullah I, Badshah H, Naseer MI, Lee HY, Kim MO. Thymoquinone and vitamin C attenuates pentylenetetrazole-induced seizures via activation of GABA B1 receptor in adult rats cortex and hippocampus. Neuromolecular Med 2015;17(1):35-46.
  • 50. Pavlova T, Stepanichev M, Gulyaeva N. Pentylenetetrazole kindling induces neuronal cyclin B1 expression in rat hippocampus. Neurosci Lett 2006;392(1-2):154-8.
Primary Language en
Subjects Science
Journal Section Research Articles
Authors

Orcid: 0000-0003-1870-229X
Author: Savaş USTUNOVA
Institution: BEZMİALEM VAKIF ÜNİVERSİTESİ TEMEL TIP BİLİMLERİ BÖLÜMÜ FİZYOLOJİ ANABİLİM DALI
Country: Turkey


Orcid: 0000-0002-0973-4305
Author: İsmail MERAL (Primary Author)
Institution: BEZMİALEM VAKIF ÜNİVERSİTESİ TEMEL TIP BİLİMLERİ BÖLÜMÜ FİZYOLOJİ ANABİLİM DALI
Country: Turkey


Orcid: 0000-0003-2335-412X
Author: Abdurrahim KOÇYİĞİT
Institution: BEZMİALEM VAKIF ÜNİVERSİTESİ TEMEL TIP BİLİMLERİ BÖLÜMÜ TIBBİ BİYOKİMYA ANABİLİM DALI
Country: Turkey


Orcid: 0000-0002-8593-1415
Author: Aysu KILIC
Institution: BEZMİALEM VAKIF ÜNİVERSİTESİ TEMEL TIP BİLİMLERİ BÖLÜMÜ FİZYOLOJİ ANABİLİM DALI
Country: Turkey


Orcid: 0000-0002-4554-3995
Author: Oyku ZEYBEK
Institution: BEZMİALEM VAKIF ÜNİVERSİTESİ TEMEL TIP BİLİMLERİ BÖLÜMÜ FİZYOLOJİ ANABİLİM DALI
Country: Turkey


Orcid: 0000-0002-7100-9817
Author: Mehmet ÜYÜKLÜ
Institution: SİİRT ÜNİVERSİTESİ TEMEL TIP BİLİMLERİ BÖLÜMÜ FİZYOLİ ANABİLİM DALI
Country: Turkey


Orcid: 0000-0002-1393-3235
Author: Sedat MEYDAN
Institution: BEZMİALEM VAKIF ÜNİVERSİTESİ TEMEL TIP BİLİMLERİ BÖLÜMÜ ANATOMİ ANABİLİM DALI
Country: Turkey


Supporting Institution This work was supported by the Research Fund of Bezmialem Vakif University.
Project Number 6.2013/8
Dates

Application Date : October 12, 2020
Acceptance Date : November 11, 2020
Publication Date : December 25, 2020

Bibtex @correction { iufsjb809351, journal = {European Journal of Biology}, issn = {2602-2575}, eissn = {2618-6144}, address = {}, publisher = {Istanbul University}, year = {2020}, volume = {79}, pages = {124 - 131}, doi = {}, title = {Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats}, key = {cite}, author = {Ustunova, Savaş and Meral, İsmail and Koçyiğit, Abdurrahim and Kılıc, Aysu and Zeybek, Oyku and Üyüklü, Mehmet and Meydan, Sedat} }
APA Ustunova, S , Meral, İ , Koçyiğit, A , Kılıc, A , Zeybek, O , Üyüklü, M , Meydan, S . (2020). Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats . European Journal of Biology , 79 (2) , 124-131 . Retrieved from https://dergipark.org.tr/en/pub/iufsjb/issue/55111/809351
MLA Ustunova, S , Meral, İ , Koçyiğit, A , Kılıc, A , Zeybek, O , Üyüklü, M , Meydan, S . "Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats" . European Journal of Biology 79 (2020 ): 124-131 <https://dergipark.org.tr/en/pub/iufsjb/issue/55111/809351>
Chicago Ustunova, S , Meral, İ , Koçyiğit, A , Kılıc, A , Zeybek, O , Üyüklü, M , Meydan, S . "Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats". European Journal of Biology 79 (2020 ): 124-131
RIS TY - JOUR T1 - Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats AU - Savaş Ustunova , İsmail Meral , Abdurrahim Koçyiğit , Aysu Kılıc , Oyku Zeybek , Mehmet Üyüklü , Sedat Meydan Y1 - 2020 PY - 2020 N1 - DO - T2 - European Journal of Biology JF - Journal JO - JOR SP - 124 EP - 131 VL - 79 IS - 2 SN - 2602-2575-2618-6144 M3 - UR - Y2 - 2020 ER -
EndNote %0 European Journal of Biology Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats %A Savaş Ustunova , İsmail Meral , Abdurrahim Koçyiğit , Aysu Kılıc , Oyku Zeybek , Mehmet Üyüklü , Sedat Meydan %T Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats %D 2020 %J European Journal of Biology %P 2602-2575-2618-6144 %V 79 %N 2 %R %U
ISNAD Ustunova, Savaş , Meral, İsmail , Koçyiğit, Abdurrahim , Kılıc, Aysu , Zeybek, Oyku , Üyüklü, Mehmet , Meydan, Sedat . "Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats". European Journal of Biology 79 / 2 (December 2020): 124-131 .
AMA Ustunova S , Meral İ , Koçyiğit A , Kılıc A , Zeybek O , Üyüklü M , Meydan S . Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats. Eur J Biol. 2020; 79(2): 124-131.
Vancouver Ustunova S , Meral İ , Koçyiğit A , Kılıc A , Zeybek O , Üyüklü M , Meydan S . Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats. European Journal of Biology. 2020; 79(2): 124-131.
IEEE S. Ustunova , İ. Meral , A. Koçyiğit , A. Kılıc , O. Zeybek , M. Üyüklü and S. Meydan , "Effects of Nigella sativa on Plasma Oxidative Stress, and Some Apoptotic Protein Markers in Cerebrum and Hippocampus in Pentylenetetrazol Induced-Kindling Rats", European Journal of Biology, vol. 79, no. 2, pp. 124-131, Dec. 2020