Effects of Thymus vulgaris L. in Acute and Chronic Epilepsy Models in Rats Induced by Pentylenetetrazole

The aim of this study was to investigate the effects of Thymus vulgaris L. (TVL) on oxidative stress, motor coordination and learning/memory in acute and chronic epilepsy models in rats induced by Pentylenetetrazole (PTZ). To this end, 64 male Wistar-albino rats were randomly divided into eight groups with 8 rats each: (1) acute control (AC), (2) acute PTZ (APTZ), (3) acute PTZ + sodium valproate (APTZ+VPA), (4) acute PTZ + TVL (APTZ+TVL), (5) chronic control (CC), (6) PTZ kindling (PTZk), (7) PTZ kindling + VPA (PTZk+VPA) and (8) PTZ kindling + TVL (PTZk+TVL) . Seizures were observed for 30 min after each PTZ injection and were scored. Acute PTZ-induced seizures were created by injecting a single convulsive dose of PTZ (60 mg/kg, ip) in acute groups. PTZ kindling was produced by injecting a subconvulsant dose of PTZ (35 mg/kg, ip) every other day, with 14 injections in total. No significant difference was found among the PTZk + VPA, PTZk, and PTZk + TVL groups with regard to seizure scores. No significant difference was found among all the 8 groups in the learning/memory tests conducted using the Morris Water Maze (MWM) test and the motor activity tests conducted using the rotarod test (P>0.05). The analysis of total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) indicated that the administration of PTZ decreased the antioxidant capacity and increased the oxidant capacity. Moreover, the TVL administration established the oxidant/antioxidant balance, particularly in the chronic groups. Further studies are needed to investigate whether high doses of TVL have an effect on PTZ-induced seizure scores.

Sıçanlarda Pentilentetrazol İle İndüklenen Akut ve Kronik Epilepsi Modellerinde Thymus vulgaris L.’nin Etkileri

Bu çalışmanın amacı pentilentetrazol ile indüklenen akut ve kronik epilepsi modellerinde Thymus vulgaris L. (TVL)’in oksidatif stres, motor koordinasyon ve öğrenme/bellek üzerine etkilerini araştırmaktır. Bu amaçla 64 adet Wistar albino sıçan randomize olarak sekiz gruba ayrıldı. (1) akut kontrol (AC), (2) akut pentilentetrazol (APTZ) (3) akut PTZ + sodyum valproat (APTZ+VPA), (4) akut PTZ + TVL (APTZ+TVL), (5) kronik kontrol (CC), (6) PTZ tutuşma (PTZk), (7) PTZ tutuşma + VPA (PTZk+VPA) ve (8) PTZ tutuşma + TVL (PTZk + TVL). PTZ enjeksiyonundan sonra 30 dk boyunca nöbetler gözlenerek skorlandı. Çalışmada tek doz PTZ (60 mg/kg, ip) enjeksiyonu ile akut PTZ indüklü nöbet modeli oluşturuldu. Tutuşma ise gün aşırı subkonvulsan dozda PTZ (35 mg/kg, ip) uygulanarak toplam 14 enjeksiyonla oluşturuldu. PTZk+VPA, PTZk ve PTZk+TVL grupları arasında nöbet skorları bakımından anlamlı bir fark bulunamadı. Kronik çalışma gruplarında Morris water maze cihazı ile yapılan öğrenme ve bellek testleri yanında rota rod cihazı ile yapılan motor aktivite testlerinde gruplar arasında farklılık görülmedi (P>0.05). Total antioksidan statüsü (TAS), total oksidan statüsü (TOS) ve oksidatif stres indeksi (OSİ) sonuçları, PTZ uygulaması neticesinde antioksidan kapasitenin azaldığı, oksidan kapasitenin ise arttığı belirlendi. T. vulgaris’in özellikle uzun süre uygulanması ile total oksidanantioksidan dengenin sağlandığı görüldü. Sonuç olarak gelecekte, daha yüksek dozlarda T. vulgaris L.’nin PTZ indüklü nöbet skorlarını değiştirip değiştirmeyeceğini belirlenmesi için ek çalışmaların yapılabileceği düşünülmektedir.

___

1. Pitkanen A, Sutula TP: Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal lobe epilepsy. Lancet Neurol, 1 (3): 173-181, 2002. DOI: 10.1016/S1474-4422(02)00073-X

2. Altıntaş A: Nöroinflamasyon, İmmun Mekanizmalar ve Epilepsi. Türk Farmakoloji Derneği 22. Ulusal Farmakoloji Kongresi. 4-7 Kasım, Antalya, Bildiri Özet Kitabı: 35-36, 2013.

3. Löscher W: Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy. Epilepsy  Res, 50 (1-2): 105-123, 2002. DOI: 10.1016/S09201211(02)00073-6

4. Onat F: Antiepileptik ilaç hedefi olarak İnflamasyon. Türk Farmakoloji Derneği 22. Ulusal Farmakoloji Kongresi. 4-7 Kasım, Antalya, Bildiri Özet Kitabı: 37-38, 2013.

5. Akarsu E: Sistematik inflamatuar yanıt ve nöronal eksitabilite. Türk Farmakoloji Derneği 22. Ulusal Farmakoloji Kongresi. 4-7 Kasım, Antalya, Bildiri Özet Kitabı: 39-40, 2013.

6. Vezzani A, Bartfai T, Bianchi M, Rossetti C, French J: Therapeutic potential of new antiinflammatory drugs. Epilepsia, 52 (S8): 67–69, 2011. DOI: 10.1111/j.1528-1167.2011.03242.x

7. Baytop T, Başer KHC, Kırımer N: Türkiye’de Bitkilerle Tedavi. İstanbul Üniversitesi, Eczacılık Fakültesi Yayınları, No. 3255. İstanbul Bitkisel İlaç Hammaddeleri Toplantısı, Bildiriler, 29-31 Mayıs 2002, Eskişehir, 434-457, 1984.

8. Özcan M, Chalchat JC: Aroma profile of Thymus vulgaris L. Growing wild in Turkey. Bulg J Plant Physiol, 30 (3-4): 68-73, 2004.

9. Gençaslan G: Türkiye’de Tıbbi Amaçlı Kullanılan Bazı Bitkilerin Antioksidan Etkilerinin Taranması. Yüksek Lisans Tezi, Ankara Üniv. Sağlık Bil. Enst., 2007.

10. Fakıllı O, Özgüven M: Inventory of researches on thyme (Thymus vulgaris L) in Turkey. ÇÜ Fen Mühendislik Bil Derg, 27 (3): 54-66, 2012.

11. Prasanth RV, Ravi Vital K, Varsha P, Satyan S: Review on Thymus vulgaris traditional uses and pharmacological properties. Med Aromat Plants, 3 (3): 164-167, 2014. DOI: 10.4172/2167-0412.1000164

12. Akkol EK, Avci G, Kucukkurt I, Keles H, Tamer U, Ince S, Yesilada E: Cholesterol-reducer, antioxidant and liver protective effects of Thymbra spicata L. var. spicata. J Ethnopharmacol, 126, 314-319, 2009. DOI: 10.1016/ j.jep.2009.08.020

13. Koparal AT, Zeytinoğlu M: Effects of carvacrol on a human non-small cell lung cancer (NSCLC) cell line A549. Cytotechnolog, 43, 149-154, 2003.

14. Dikilidal M: STZ ile diyabet oluşturulmuş ratlarda kekik (Thymus vulgaris L.) ve karabaş kekiğinin (Thymbra spicata L.) kan glikoz düzeyine, kilo değişikliğine ve öğrenmeye etkisi. Yüksek Lisans Tezi, Van YYÜ Sağlık Bil. Enst., 2013.

15. Manoharan S,  Guillemin GJ,  Abiramasundari RS,  Essa MM,  Akbar M,  Akbar MD: Role of reactive oxygen species in the pathogenesis of  alzheimer’s  disease,parkinson’s  disease, and huntington’s  disease: A mini review. Oxid Med Cell Longev, 2016:8590578, 2016. DOI: 10.1155/ 2016/8590578

16. Ali BH, Blunden G: Pharmacological and toxicological properties of Nigella sativa. Phytother Res, 17, 299-305, 2003. DOI: 10.1002/ptr.1309

17. Eddouks M, Maghrani M, Zeggwagh NA, Michel J: Study of the hypoglycaemic activity of Lepidium sativum L. aqueous extract in normal and diabetic rats, J Ethnopharmacol, 97, 391-395, 2005. DOI: 10.1016/j. jep.2004.11.030

18. Patsoukis N, Zervoudakis G, Panagopoulos N, Georgiou CD, Angelatou F, Matsokis NA: Thiol redox state (TRS) and oxidative stress in the mouse hippocampus after pentylenetetrazol-induced epileptic seizure.  Neurosci Lett,  357 (2): 83-86, 2004. DOI: 10.1016/j.neulet.2003.10.080

19. Ilhan A, Iraz M, Kamisli S, Yigitoglu R: Pentylenetetrazol-induced kindling seizure attenuated by Ginkgo biloba extract (EGb 761) in mice.  Prog Neuropsychopharmacol Biol Psychiatry,  30 (8): 1504-1510, 2006. DOI: 10.1016/j.pnpbp.2006.05.013

20. Racine RJ: Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol, 32, 281–294, 1972. DOI: 10.1016/0013-4694(72)90177-0

21. Rajabzadeh A, Bideskan AE, Fazel A, Sankian M, Rafatpanah H, Haghir H: The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats. J Biomed Sci, 19:56, 2012. DOI: 10.1186/1423-0127-19-56

22. Morris RGM, Garrud P, Rawlins JNP, O’Keefe J: Place navigation impaired in rats with hippocampal lesions. Nature, 297, 681-683, 1982. DOI: 10.1038/297681a0

23. Terry AV: Spatial Navigation (Water Maze) Tasks. In, Buccafusco JJ (Ed): Source Methods of Behavior Analysis in Neuroscience. 2nd ed., Chapter 13, 153-166, Boca Raton (FL): CRC Press/Taylor & Francis, 2009.

24. Tuzcu M, Baydas G: Effect of melatonin and vitamin E on diabetesinduced learning and memory impairment in rats. Eur J Pharmacol, 537 (13): 106-110, 2006. DOI: 10.1016/j.ejphar.2006.03.024

25. Erel O: A new automated coloremetric method for measuring total oxidant status. Clin Biochem, 38, 1103-1111, 2005. DOI: 10.1016/j.clinbiochem. 2005.08.008

26. Kurt M, Çelik S, Kesim Y: Motor eşgüdümde dopaminerjik sistemin rolü.  OMÜ Tıp Derg, 19, 15-24, 2002.

27. Pearson-Smith JN, Patel M: Metabolic dysfunction and  oxidative stress  in  epilepsy. Int J Mol Sci, 18 (11): pii:E2365, 2017. DOI: 10.3390/ ijms18112365

28. Aguiar CCT, Almeida AB, Araujo PVP, de Abreu RNDC, Chaves EMC, do Vale OC, Macêdo DS, Woods DJ, Fonteles MM, Vasconcelos SMM: Oxidative stress and epilepsy: Literature review.  Oxid Med Cell Longev, 2012:795259, 2012. DOI: 10.1155/2012/795259

29. Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR: Estimation of the burden of active and lifetime epilepsy: a metaanalytic approach. Epilepsia, 51 (5): 883-890, 2010. DOI: 10.1111/j.15281167.2009.02481.x

30. Rabiei Z: Anticonvulsant effects of medicinal plants with emphasis on mechanisms of action.  Asian Pac J Trop Biomed, 7 (2): 166-172, 2017. DOI: 10.1016/j.apjtb.2016.11.028

31. Birben E, Sahiner U, Sackesen C, Erzurum S, Kalayci O: Oxidative stress and antioxidant defense.  World Allergy Organ J,  5 (1): 270, 2012.

32. Li G, Bauer S, Nowak M, Norwood B, Tackenberg B, Rosenow F, Knake S, Oertel WH, Hamer HM: Cytokines and epilepsy.  Seizure, 20 (3): 249-256, 2011. DOI: 10.1016/j.seizure.2010.12.005

33. Ergül Erkeç O, Arihan O: Pentylenetetrazol kindling epilepsy model. Epilepsi,  21 (1): 6-12, 2015. DOI: 10.5505/epilepsi.2015.08108

34. Martinc B, Grabnar I, Vovk T: The role of reactive species in epileptogenesis and influence of antiepileptic drug therapy on oxidative stress.  Curr Neuropharmacol, 10 (4): 328-343, 2012.

35. Kong Q, Lin CLG: Oxidative damage to RNA: Mechanisms, consequences, and diseases. Cell Mol Life Sci, 67 (11): 1817-1829, 2010. DOI: 10.1007/ s00018-010-0277-y

36. Lan J, Henshall DC, Simon RP, Chen J: Formation of the base modification 8-hydroxyl-2’-deoxyguanosine and DNA fragmentation following seizures induced by systemic kainic acid in the rat. J Neurochem,  74, 302309, 2000. DOI: 10.1046/j.1471-4159.2000.0740302.x

37. Tan D, Manchester LC, Reiter RJ, Qi W, Kim SJ, El-Sokkary GH: Melatonin protects hippocampal neurons in vivo against kainic acidinduced damage in mice.  J Neurosci Res, 54, 382–389,  1998. DOI: 10.1002/ (SICI)1097-4547(19981101)54:3<382::AID-JNR9>3.0.CO;2-Y

38.Gupta RC, Milatovic D, Zivin M, Dettbarn WD: Seizure-induced changes in energy metabolites and effects of N-tert-butyl-alpha-phenylnitrone (PNB) and vitamin E in rats.  Eur J Physiol, 440, R160-R162,  2000. DOI: 10.1007/ s004240000047

39. Aboul Ezz HS, Khadrawy YA, Noor NA: 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): 2195-204, 2011. DOI: 10.1007/s11064-011-0544-9

40. Taiwe GS, Moto FCO, Ayissi ERM, Ngoupaye GT, Njapdounke JSK, Nkantchoua GCN, Kouemou N, Omam JPO, Kandeda AK, Pale S, Pahaye D, Ngobum E: Effects of a lyophilized aqueous extract of Feretia apodanthera Del. (Rubiaceae) on pentylenetetrazole-induced kindling, oxidative stress, and cognitive impairment in mice. Epilepsy Behav, 43, 100108, 2015. DOI: 10.1016/j.yebeh.2014.11.022

41. Rathor N, Arora T,  Manocha S,  Patil AM,  Mediratta P,  Sharma KK: Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice. J Pharm Pharmacol, 66 (3): 477-485, 2014. DOI: 10.1111/ jphp.12181

42. Addaea JI, Pingal R, Walkins K, Cruickshank R, Youssef FF, Nayak SB: Effects of Jasminum multiflorum leaf extract on rodent models of epilepsy, motor coordination and anxiety. Epilepsy Res, 131, 58-63, 2011. DOI: 10.1016/j.eplepsyres.2017.02.012

43. Kandeda AK, Taiwe GS,  Moto FCO,  Ngoupaye GT,  Nkantchoua GCN,  Njapdounke JSK,  Omam JPO,  Pale S,  Kouemou N,  Ngo Bum EN: Antiepileptogenic and neuroprotective effects of  Pergularia daemia  on pilocarpine model of epilepsy. Front Pharmacol, 8:440, 2017. DOI: 10.3389/ fphar.2017.00440

44. Zhen J, Chang Y, Qu Z, Fu T, Liu J, Wang W: Luteolin rescues pentylenetetrazole-induced cognitive impairment in epileptic rats by reducing oxidative stress and activating PKA/CREB/BDNF signaling. Epilepsy Behav, 57, 177-184, 2016. DOI: 10.1016/j.yebeh.2016.02.001

45. Skalicka-Woźniak K, Walasek M, Aljarba TM, Stapleton P, Gibbons S, Xiao J, Łuszczki J: The anticonvulsant and anti-plasmid conjugation potential of Thymus vulgaris chemistry: An in vivo murine and in vitro study.  Food Chem Toxicol,  120, 472-478, 2018. DOI:  10.1016/j.fct.2018.07.045

46. Okay Tİ, Kısa C, Dilbaz N: Psikiyatrik bozukluklarda valproat kullanımı. Klinik Psikiyatri, 5, 33-41, 2002.

47. Abdelgadir AB, El- Hadiyah TMH: Assessment of the anticonvulsant effect of Thymus vulgaris plant. 2017. http://mmacpanel.delta.edu.sd/ includes/magazines/pdf/1_6_7.pdf; Accessed: 28.01.2019.

48. Gao B, Wu Y, Yang Y, Li W, Dong K, Zhou J, Yin Y, Huang DK, Wu WN: Sinomenine exerts anticonvulsant profile and neuroprotective activity in pentylenetetrazole kindled rats: Involvement of inhibition of NLRP1 inflammasome. J Neuroinflammation, 15:152, 2018. DOI: 10.1186/s12974018-1199-0

49.  Kaur H, Patro I, Tikoo K, Sandhir R: Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy:  Neurochem Int,  89, 40-50, 2015. DOI: 10.1016/j.neuint.2015.07.009

50. Eddy CM, Rickards HE, Cavanna AE:  The cognitive impact of antiepileptic drugs.  Ther Adv Neurol Disord,  4, 385-407, 2011. DOI: 10.1177/ 1756285611417920

51. Morteza-Semnani K, Mahmoudi M, Riahi G: Effects of essential oils and extracts from certain Thymus. Species on swimming performance in mice. Pharm Biol, 45 (6): 464-467, 2007. DOI: 10.1080/13880200701389177

52. Akan Z, Dikilidal M, Özdemir H, Oto G, Yilmaz A: Effects of Thymus vulgaris L. and Thymbra spicata L. on diabetes mellitus associated cognitive impairment and neuropathy: Thymus vulgaris and cognitive function improvements. Med Sci Discov, 1 (1): 16-21, 2014.

53. Hamm RJ, Pike BR, O›Dell DM, Lyeth BG, Jenkins LW: The rotarod test: An evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma, 11 (2): 187-96, 1994. DOI: 10.1089/ neu.1994.11.187
Kafkas Üniversitesi Veteriner Fakültesi Dergisi-Cover
  • ISSN: 1300-6045
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 1995
  • Yayıncı: Kafkas Üniv. Veteriner Fak.
Sayıdaki Diğer Makaleler

Tip O/BY/CHA/2010 Şap Hastalığı Virusuna Karşı Artırılmış Duyarlılıkta Süt Emen Fare αυβ8 Transgenik CHO-677 Hücre Hattının Oluşturulması ve Değerlendirilmesi

Fan YANG, Kaiqi LIAN, Lingling ZHOU, Mingliang ZHANG, Yuwei SONG

Türkiye’de Perakende Dana Eti Fiyatlarındaki Değişimin Garch Yöntemiyle Belirlenmesi, 2014-2017

Mehmet Saltuk ARIKAN, Ahmet Cumhur AKIN, Mustafa Bahadır ÇEVRİMLİ, Mustafa Agah TEKİNDAL

Antimicrobial Susceptibility, Serotypes, and Genetic Diversity of Streptococcus suis in Diseased and Healthy Pigs in Southern China

Ling PENG, Chongbo XU, Xufu YANG, Boting LIU

Efficacy of Topical Curcuma longa and Nigella sativa Combination for Feline Head and Neck Dermatitis: An Open Pilot Study

Kerem URAL, MEHMET GÜLTEKİN, Hasan ERDOĞAN

Etlik Piliçlerde Diyetteki Yağ Asitlerinin Büyüme Performansı, Karkas Özellikleri, Yağ Asidi Profili ve Serum Biyokimyasal Parametreleri Üzerine Etkisi

Branko MILANKOVIĆ, Milena KRSTIĆ, Dragan ŠEFER, Radmila MARKOVIĆ, Jelena ĆIRIĆ, Branislav BALTIĆ, Vesna ĐORĐEVIĆ, Marija STARČEVIĆ, Milka POPOVIĆ

Establishment and Evaluation of a Suckling Mouse Integrin αυβ8 Transgenic CHO-677 Cell Line with Increased Susceptibility to Type O/BY/CHA/2010 Foot-and-Mouth Disease Virus

Kaiqi LIAN, Fan YANG, Lingling ZHOU, Mingliang ZHANG, Yuwei SONG

Ventral Hernilerin Onarımında Polyester Film Kullanımının Erken ve İleri Dönem Sonuçlarının Değerlendirilmesi: Tavşan Modellerinde Deneysel Bir Çalışma

Berna ERSöz KANAY, Serpil DAĞ, Mustafa GöK, Engin KILIÇ, Sadık YAYLA, Celal Şahin ERMUTLU, Vedat BARAN, Kemal KILIÇ

Arı Spermasının Protein Eklenmiş TL-Hepes Bazlı Sulandırıcı İle Dondurulması

Zekariya NUR, Hasan ŞEN, Selvinar ÇAKMAK, Selim ALÇAY, Emine MÜLKPINAR, Mehmed Berk TOKER, Burcu ÜSTÜNER, İbrahim ÇAKMAK

Growth Performance and Meat Quality in Tibetan Sheep Fed Diets Differing in Type of Forage

Ao REN, Bin LI, Hong-dong JIE, Liang CHEN, Bin ZHANG, Si-man AO, Zhi-liang TAN, Chuan-she ZHOU, Ba-sang ZHUZHA, Xiao-ying CHEN, Sheng-zhen HOU

Kedi Baş ve Boyun Dermatitisi İçin Topikal Curcuma longa ve Nigella sativa Kombinasyonunun Etkinliği: Açık Pilot Çalışma

Mehmet GÜLTEKİN, Hasan ERDOĞAN, Kerem URAL