Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde İncelenmesi

Arzuhan Çetindağ Çiltaş; Bilal Şahin

doi:10.46332/aemj.831240

Research Article

Investigation of the Effect of Folic Acid on Ethosuximide in Pentylenetetrazole-Induced Acute Seizures in Mice

Year 2022, Volume: 6 Issue: 2, 154 - 161, 30.08.2022

Arzuhan Çetindağ Çiltaş Bilal Şahin

https://doi.org/10.46332/aemj.831240

Abstract

Purpose: Epilepsy is one of the most prevalent neurological diseases today. Despite various treatments, there is still no complete seizure control. Studies have shown the positive effects of folic acid (FA) and its derivatives on seizures. The objective of this study is to investigate Caspase-3 and TOS activity in brain tissues as well as the effect of folic acid on ethosuximide (ETX) in mice with pentylenetetrazol-induced seizures.

Materials and Methods: In this study, 30 mice of BALB/c species were divided randomly into 5 groups: Control; pen-tylenetetrazol (PTZ); PTZ-induced seizure group; FA in which 3 mg/kg FA and PTZ were administered for 7 days; ETX in which 50 mg/kg ETX and PTZ were administered for 7 days; FA+ ETX in which 3 mg/kg FA and 50 mg/kg ETX and PTZ were administered for 7 days. The brain tissues of all mice were dissected, then the cortex and hippocampus were separated 24 hours after PTZ application.

Results: FA, ETX and FA+ETX groups significantly decreased the seizure stage compared to the PTZ group, and similarly prolonged the first myoclonic jerk times, but the FA and FA+ETX groups were found to decrease the onset of generalizedtonic–clonic seizures (p<0.05). However, the FA and FA+ETX groups decreased the hippocampal TOS levels. (p<0.05). Similarly, hippocampal caspase-3 levels were lower in the FA group (p<0.05).

Conclusion: FA can be a useful therapeutic agent for the treatment of epilepsy with its antioxidant and antiapoptotic properties. The synergistic effect of FA with ETX can promote its protective effect against neuronal damage

Keywords

ethosuximide, folic acid, pentylenetetrazole (PTZ)

References

1. Owoalade SA, Lou D.M.M, Yadav K, Poudel S. A Review on anti-epileptic activity of seaweed Ecklonia cava. Drug Deliv J. 2019;9(1):425-432.
2. EE Altay, E Bilir, C İrkeç. Demans ve epilepsi. Demans Dizisi. 1999;1(4):116-128.
3. Meldrum BS, Akbar MT, Chapman AG. Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res. 1999;36(2-3):189-204.
4. Gunes H, Ozdemir E, Arslan G. Coenzyme Q10 increases absence seizures in WAG/Rij rats: The role of the nitric oxide pathway. Epilepsy Res. 2019;154:69-73.
5. Kandratavicius L, Balista P, Lopes-Aguiar C, et al. Animal models of epilepsy: use and limitations Neuropsychiatr Dis. Treat. 2014;10:1693-1705.
6. Shibata N, Kobayashi M. The role for oxidative stress in neurodegenerative diseases Brain Nerve. 2008;60(2):157- 170.
7. Aguiar C.C.T, Almeida A.B, Araújo P.V.De Abreu P.R.V, et al. Oxidative stress and epilepsy: literature review Oxid. Med. Cell. Longev. 2012;1-12.
8. Waldbaum S, Patel M. Mitochondria, oxidative stress, and temporal lobe epilepsy Epilepsy Res. 2010;88(1):23-45.
9. Naziroǧlu M, Akay M.B, Çelik Ö, Yildirim M.I, Balci E, Yürekli V.A. Capparis ovata modulates brain oxidative toxicity and epileptic seizures in pentylentetrazol-induced epileptic rats. Neurochem. Res. 2013;38(4):780-788.
10. Fava M, Mischoulon D. Folate in depression: efficacy, safety, differences in formulations, and clinical issues. J Clin Psychiatry. 2009;70(5):12–17.
11. Hamid A, Wani NA, Kaur J. New perspectives on folate transport in relation to alcoholism-induced folate malabsorption--association with epigenome stability and cancer development. FEBS J. 2009;276(8):2175-2191.
12. Brocardo PS, Budni J, Lobato KR, Santos ARS, Rodrigues ALS. Evidence for the involvement of the opioid system in the antidepressant-like effect of folic acid in the mouse forced swimming test. Behav Brain Res. 2009;200(1):122-127.
13. Djurić E, Hrnčić D, Šutulović N, et all. Folic acid supplementation alleviates behavioral manifestations of lindaneinduced seizuress. Arch Biol Sci. 2019;71(3):403-408.
14. Sarna LK, Wu N, Wang P, Hwang S-Y, Siow YL, O K. Folic acid supplementation attenuates high fat diet induced hepatic oxidative stress via regulation of NADPH oxidase. Can J Physiol Pharmacol. 2012;90(2):155-165.
15. Matté C, Mackedanz V, Stefanello FM, et al. Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid. Neurochem Int. 2009;54(1):7-13.
16. Taştemur Y, Gumus E, Ergül M, et al. Positive effects of angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole-induced epileptic seizures in mice. Tropıcal Journal Of Pharmaceutıcal Research. 2020;19(3):637-643.
17. Racine, RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 1972;32(3):281-294.
18. Erdogan MA, Yusuf D, Erdogan A, Erbas O. Levodropropizine suppresses seizure activity in rats with pentylenetetrazol-induced epilepsy. Epilepsy Res. 2019;150:32– 37.
19. Kaminski RM, Tochman AM, Dekundy A, Turski WA, Czuczwar SJ. Ethosuximide and valproate display high efficacy against lindane-induced seizures in mice. Toxicol Lett. 2004;154(1-2):55-60.
20. Oyama K, Sugimura Y, Murase T, et al. Folic acid prevents congenital malformations in the offspring of diabetic mice. Endocr J. 2009;56(1):29-37.
21. Ernst O, Zor T. Linearization of the bradford protein assay. J Vis Exp. 2010;12(38):1918.
22. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37(2):112-119.
23. Chakravarthy N, Tsakalis K, Sabesan S, Iasemidis L. Homeostasis of brain dynamics in epilepsy: a feedback control systems perspective of seizures. Ann Biomed Eng. 2009;37(3):565-585.
24. Taskıran AS, Ozdemir E, Gumus E, Ergul M. The effects of salmon calcitonin on epileptic seizures, epileptogenesis, and postseizure hippocampal neuronal damage in pentylenetetrazole-induced epilepsy model in rats. Epilepsy Behav. 2020;113:107501.
25. Babycha L, Valte V (2018). Anticonvulsant activity of aqueous extract of Eupatorium birmanicum DC. Leaves on seizure induced by PTZ in albino mice, alone and in combination with ethosuximide. Int J Pharm Sci Res. 2018;9(5):2048-2052.
26. Chen SD, Yeh KH, Huang YH, Shaw FZ (2011). Effect of intracranial administration of ethosuximide in rats with spontaneous or pentylenetetrazol-induced spike-wave discharges. Epilepsia. 2011;52(7):1311-1318.
27. Beal, M.F. Mitochondrial dysfunction in neurodegenerative diseases. Biochim. Biophys. Acta. 1998;1366(1- 2):211-223.
28. Mariani E, Polidori MC, Cherubini A, Mecocci P. Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;827(1):65-75.
29. Kazmi Z, Zeeshan S, Khan A, et al. Anti-epileptic activity of daidzin in PTZ-induced mice model by targeting oxidative stress and BDNF/VEGF signaling. Neurotoxicology. 2020;79:150-163.
30. Shin EJ, Jeong JH, Chung YH, et al. Role of oxidative stress in epileptic seizures. Neurochem Int. 2011;59(2):122-137.
31. Djukic A. Folate-responsive neurologic diseases. Pediatr Neurol. 2007;37(6):387-397.
32. Cuskelly GJ, McNulty H, Scott JM. Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects. Lancet. 1996;347(9002):657- 659.
33. Peleg-Raibstein D, Luca E, Wolfrum C. Maternal highfat diet in mice programs emotional behavior in adulthood. Behav Brain Res. 2012;233(2):398-404.
34. Hyland K, Smith I, Bottiglieri T, et al. Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency. Neurology. 1988; 38(3):459-462.
35. Seker FB, Yorulmaz H, Kaptan E, Caglayan B, Oztas B. Gestational treatment of folic acid attenuates blood-brain barrier leakage in pregnant- and prepubertal rats after pentylenetetrazole-induced seizure. Nutr Neurosci. 2016;19(2):55-62.
36. Antoniades C, Shirodaria C, Warrick N, et al.5methyltetrahy drofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation. 2006;114(11):1193-1201.
37. Cano MJ, Ayala A, Murillo ML, Carreras O. Protective effect of folic acid against oxidative stress produced in 21- day postpartum rats by maternal-ethanol chronic consumption during pregnancy and lactation period. Free Radic Res. 2001;34(1):1–8.
38. Girotto F, Scott L, Avchalumov Y, et al. High dose folic acid supplementation of rats alters synaptic transmission and seizure susceptibility in offspring. Sci Rep. 2013;3 (1):1465.
39. Wang P, Ren R.N, Caı S.Y, Chen X.M, Ye L.Y. Influence of folic acid on the protective role of topiramate against neuronal damage in immature rats. Chinese Journal of Contemporary Pediatrics. 2008;26(2):96.
40. Wang P, Ren R.N, Caı S.Y, Chen X.M, Ye L.Y. Neuroprotective effects of topiramate and folic acid on young rats with kindling-induced epilepsy. Chinese Journal of Contemporary Pediatrics. 2008;10(1):65-69.
41. Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D, Rodríguez-Martínez E, Yescas Gómez P. Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy. Oxid Med Cell Long. 2014;2014: 293689.
42. Faherty CJ, Xanthoudakis S, Smeyne RJ. Caspase-3–dependent neuronal death in the hippocampus following kainic acid treatment. Mol Brain Res. 1999;70(1):159-163.
43. Ali AE, Mahdy HM, Elsherbiny DM, Azab SS. Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent hippocampal damage and memory deficit in rats: Impact on oxidative, inflammatory and apoptotic machineries. Biochem Pharmacol. 2018;156:431‐443.
44. Zhang X, Chen S, Li L, Wang Q, Le W. Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1 G93A transgenic mice. Neuropharmacology. 2008;54(7):1112-1119.
45. Ho PI, Ashline D, Dhitavat S, et al. Folate deprivation induces neurodegeneration: roles of oxidative stress and increased homocysteine. Neurobiol Dis. 2003;14(1):32- 42.

Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde İncelenmesi

Year 2022, Volume: 6 Issue: 2, 154 - 161, 30.08.2022

Arzuhan Çetindağ Çiltaş Bilal Şahin

https://doi.org/10.46332/aemj.831240

Abstract

Amaç: Epilepsi, günümüzde en sık görülen nörolojik hastalıklardan biridir. Çeşitli tedavilere rağmen hala tam olarak nöbet kontrolü sağlanamamaktadır. Yapılan çalışmalar folik asit (FA) ve türevlerinin nöbetler üzerine olumlu etkiler ortaya koymuştur. Bu çalışmanın amacı, farelerde pentilentetrazol ile oluşturulan nöbet-lerde folik asitin etosüksimid üzerine etkisinin yanında beyin dokularında kaspaz-3 ve TOS aktivitesini araştırmaktır.

Araçlar ve Yöntem: Çalışmada BALB/c türü 30 fare rastgele 5 gruba ayrıldı: Kontrol, pentilentetrazol (PTZ); PTZ ile nöbet indüklenen grup, FA; 7 gün boyunca 3 mg/kg verilen ve PTZ uygulanan grup, etosüksimid; 7 gün boyunca 50 mg/kg verilen ve PTZ uygulanan grup, FA+ etosüksimid; 7 gün boyunca 3 mg/kg FA ve 50 mg/kg etosüksimid verilen ve PTZ uygulanan grup. PTZ uygulamasından 24 saat sonra tüm farelerin beyin dokuları çıkarıldı, korteks ve hipokampus ayrıldı.

Bulgular: Folik asit, etosüksimid ve FA+ etosüksimid grupları PTZ grubuna göre nöbet evresini anlamlı olarak azalttı, benzer şekilde first miyoklonik jerk sürelerini uzattı ancak jeneralize tonik-klonik nöbete giriş zamanını FA ve FA+ etosüksimid gruplarının azalttığı bulundu (p<0.05). Bununla birlikte FA ve FA+ etosüksimid grupları, hipokampal TOS seviyesini azalttı. (p<0.05). Benzer şekilde, hipokampal kaspaz-3 seviyesi FA uygulanan grupta daha düşük bulundu (p<0.05).

Sonuç: FA antioksidatif ve antiapoptotik özellikleriyle epilepsi tedavisi için faydalı bir terapotik ajan olabilir. Folik asit, etosüksimid ile sinerjik etkisi nöronal hasara karşı koruyucu etkisini güçlendirebilir.

Keywords

etosüksimid, folik asit, pentilentetrazol (PTZ)

References

1. Owoalade SA, Lou D.M.M, Yadav K, Poudel S. A Review on anti-epileptic activity of seaweed Ecklonia cava. Drug Deliv J. 2019;9(1):425-432.
2. EE Altay, E Bilir, C İrkeç. Demans ve epilepsi. Demans Dizisi. 1999;1(4):116-128.
3. Meldrum BS, Akbar MT, Chapman AG. Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res. 1999;36(2-3):189-204.
4. Gunes H, Ozdemir E, Arslan G. Coenzyme Q10 increases absence seizures in WAG/Rij rats: The role of the nitric oxide pathway. Epilepsy Res. 2019;154:69-73.
5. Kandratavicius L, Balista P, Lopes-Aguiar C, et al. Animal models of epilepsy: use and limitations Neuropsychiatr Dis. Treat. 2014;10:1693-1705.
6. Shibata N, Kobayashi M. The role for oxidative stress in neurodegenerative diseases Brain Nerve. 2008;60(2):157- 170.
7. Aguiar C.C.T, Almeida A.B, Araújo P.V.De Abreu P.R.V, et al. Oxidative stress and epilepsy: literature review Oxid. Med. Cell. Longev. 2012;1-12.
8. Waldbaum S, Patel M. Mitochondria, oxidative stress, and temporal lobe epilepsy Epilepsy Res. 2010;88(1):23-45.
9. Naziroǧlu M, Akay M.B, Çelik Ö, Yildirim M.I, Balci E, Yürekli V.A. Capparis ovata modulates brain oxidative toxicity and epileptic seizures in pentylentetrazol-induced epileptic rats. Neurochem. Res. 2013;38(4):780-788.
10. Fava M, Mischoulon D. Folate in depression: efficacy, safety, differences in formulations, and clinical issues. J Clin Psychiatry. 2009;70(5):12–17.
11. Hamid A, Wani NA, Kaur J. New perspectives on folate transport in relation to alcoholism-induced folate malabsorption--association with epigenome stability and cancer development. FEBS J. 2009;276(8):2175-2191.
12. Brocardo PS, Budni J, Lobato KR, Santos ARS, Rodrigues ALS. Evidence for the involvement of the opioid system in the antidepressant-like effect of folic acid in the mouse forced swimming test. Behav Brain Res. 2009;200(1):122-127.
13. Djurić E, Hrnčić D, Šutulović N, et all. Folic acid supplementation alleviates behavioral manifestations of lindaneinduced seizuress. Arch Biol Sci. 2019;71(3):403-408.
14. Sarna LK, Wu N, Wang P, Hwang S-Y, Siow YL, O K. Folic acid supplementation attenuates high fat diet induced hepatic oxidative stress via regulation of NADPH oxidase. Can J Physiol Pharmacol. 2012;90(2):155-165.
15. Matté C, Mackedanz V, Stefanello FM, et al. Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid. Neurochem Int. 2009;54(1):7-13.
16. Taştemur Y, Gumus E, Ergül M, et al. Positive effects of angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole-induced epileptic seizures in mice. Tropıcal Journal Of Pharmaceutıcal Research. 2020;19(3):637-643.
17. Racine, RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 1972;32(3):281-294.
18. Erdogan MA, Yusuf D, Erdogan A, Erbas O. Levodropropizine suppresses seizure activity in rats with pentylenetetrazol-induced epilepsy. Epilepsy Res. 2019;150:32– 37.
19. Kaminski RM, Tochman AM, Dekundy A, Turski WA, Czuczwar SJ. Ethosuximide and valproate display high efficacy against lindane-induced seizures in mice. Toxicol Lett. 2004;154(1-2):55-60.
20. Oyama K, Sugimura Y, Murase T, et al. Folic acid prevents congenital malformations in the offspring of diabetic mice. Endocr J. 2009;56(1):29-37.
21. Ernst O, Zor T. Linearization of the bradford protein assay. J Vis Exp. 2010;12(38):1918.
22. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37(2):112-119.
23. Chakravarthy N, Tsakalis K, Sabesan S, Iasemidis L. Homeostasis of brain dynamics in epilepsy: a feedback control systems perspective of seizures. Ann Biomed Eng. 2009;37(3):565-585.
24. Taskıran AS, Ozdemir E, Gumus E, Ergul M. The effects of salmon calcitonin on epileptic seizures, epileptogenesis, and postseizure hippocampal neuronal damage in pentylenetetrazole-induced epilepsy model in rats. Epilepsy Behav. 2020;113:107501.
25. Babycha L, Valte V (2018). Anticonvulsant activity of aqueous extract of Eupatorium birmanicum DC. Leaves on seizure induced by PTZ in albino mice, alone and in combination with ethosuximide. Int J Pharm Sci Res. 2018;9(5):2048-2052.
26. Chen SD, Yeh KH, Huang YH, Shaw FZ (2011). Effect of intracranial administration of ethosuximide in rats with spontaneous or pentylenetetrazol-induced spike-wave discharges. Epilepsia. 2011;52(7):1311-1318.
27. Beal, M.F. Mitochondrial dysfunction in neurodegenerative diseases. Biochim. Biophys. Acta. 1998;1366(1- 2):211-223.
28. Mariani E, Polidori MC, Cherubini A, Mecocci P. Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;827(1):65-75.
29. Kazmi Z, Zeeshan S, Khan A, et al. Anti-epileptic activity of daidzin in PTZ-induced mice model by targeting oxidative stress and BDNF/VEGF signaling. Neurotoxicology. 2020;79:150-163.
30. Shin EJ, Jeong JH, Chung YH, et al. Role of oxidative stress in epileptic seizures. Neurochem Int. 2011;59(2):122-137.
31. Djukic A. Folate-responsive neurologic diseases. Pediatr Neurol. 2007;37(6):387-397.
32. Cuskelly GJ, McNulty H, Scott JM. Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects. Lancet. 1996;347(9002):657- 659.
33. Peleg-Raibstein D, Luca E, Wolfrum C. Maternal highfat diet in mice programs emotional behavior in adulthood. Behav Brain Res. 2012;233(2):398-404.
34. Hyland K, Smith I, Bottiglieri T, et al. Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency. Neurology. 1988; 38(3):459-462.
35. Seker FB, Yorulmaz H, Kaptan E, Caglayan B, Oztas B. Gestational treatment of folic acid attenuates blood-brain barrier leakage in pregnant- and prepubertal rats after pentylenetetrazole-induced seizure. Nutr Neurosci. 2016;19(2):55-62.
36. Antoniades C, Shirodaria C, Warrick N, et al.5methyltetrahy drofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation. 2006;114(11):1193-1201.
37. Cano MJ, Ayala A, Murillo ML, Carreras O. Protective effect of folic acid against oxidative stress produced in 21- day postpartum rats by maternal-ethanol chronic consumption during pregnancy and lactation period. Free Radic Res. 2001;34(1):1–8.
38. Girotto F, Scott L, Avchalumov Y, et al. High dose folic acid supplementation of rats alters synaptic transmission and seizure susceptibility in offspring. Sci Rep. 2013;3 (1):1465.
39. Wang P, Ren R.N, Caı S.Y, Chen X.M, Ye L.Y. Influence of folic acid on the protective role of topiramate against neuronal damage in immature rats. Chinese Journal of Contemporary Pediatrics. 2008;26(2):96.
40. Wang P, Ren R.N, Caı S.Y, Chen X.M, Ye L.Y. Neuroprotective effects of topiramate and folic acid on young rats with kindling-induced epilepsy. Chinese Journal of Contemporary Pediatrics. 2008;10(1):65-69.
41. Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D, Rodríguez-Martínez E, Yescas Gómez P. Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy. Oxid Med Cell Long. 2014;2014: 293689.
42. Faherty CJ, Xanthoudakis S, Smeyne RJ. Caspase-3–dependent neuronal death in the hippocampus following kainic acid treatment. Mol Brain Res. 1999;70(1):159-163.
43. Ali AE, Mahdy HM, Elsherbiny DM, Azab SS. Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent hippocampal damage and memory deficit in rats: Impact on oxidative, inflammatory and apoptotic machineries. Biochem Pharmacol. 2018;156:431‐443.
44. Zhang X, Chen S, Li L, Wang Q, Le W. Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1 G93A transgenic mice. Neuropharmacology. 2008;54(7):1112-1119.
45. Ho PI, Ashline D, Dhitavat S, et al. Folate deprivation induces neurodegeneration: roles of oxidative stress and increased homocysteine. Neurobiol Dis. 2003;14(1):32- 42.

There are 45 citations in total.

Details

Primary Language	Turkish
Subjects	Clinical Sciences
Journal Section	Original Articles
Authors	Arzuhan Çetindağ Çiltaş 0000-0002-5420-3546 Bilal Şahin 0000-0002-4419-1385
Early Pub Date	August 16, 2022
Publication Date	August 30, 2022
Published in Issue	Year 2022 Volume: 6 Issue: 2

Cite

APA	Çetindağ Çiltaş, A., & Şahin, B. (2022). Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde İncelenmesi. Ahi Evran Medical Journal, 6(2), 154-161. https://doi.org/10.46332/aemj.831240
AMA	Çetindağ Çiltaş A, Şahin B. Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde İncelenmesi. Ahi Evran Med J. August 2022;6(2):154-161. doi:10.46332/aemj.831240
Chicago	Çetindağ Çiltaş, Arzuhan, and Bilal Şahin. “Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol Ile Oluşturulan Akut Nöbet Modelinde İncelenmesi”. Ahi Evran Medical Journal 6, no. 2 (August 2022): 154-61. https://doi.org/10.46332/aemj.831240.
EndNote	Çetindağ Çiltaş A, Şahin B (August 1, 2022) Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde İncelenmesi. Ahi Evran Medical Journal 6 2 154–161.
IEEE	A. Çetindağ Çiltaş and B. Şahin, “Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde İncelenmesi”, Ahi Evran Med J, vol. 6, no. 2, pp. 154–161, 2022, doi: 10.46332/aemj.831240.
ISNAD	Çetindağ Çiltaş, Arzuhan - Şahin, Bilal. “Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol Ile Oluşturulan Akut Nöbet Modelinde İncelenmesi”. Ahi Evran Medical Journal 6/2 (August 2022), 154-161. https://doi.org/10.46332/aemj.831240.
JAMA	Çetindağ Çiltaş A, Şahin B. Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde İncelenmesi. Ahi Evran Med J. 2022;6:154–161.
MLA	Çetindağ Çiltaş, Arzuhan and Bilal Şahin. “Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol Ile Oluşturulan Akut Nöbet Modelinde İncelenmesi”. Ahi Evran Medical Journal, vol. 6, no. 2, 2022, pp. 154-61, doi:10.46332/aemj.831240.
Vancouver	Çetindağ Çiltaş A, Şahin B. Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde İncelenmesi. Ahi Evran Med J. 2022;6(2):154-61.

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