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Farelerde Pentilentetrazol ile Oluşturulmuş Konvülzyonda Daidzein Nöbet Oluşumunu Engeller

Yıl 2026, Cilt: 7 Sayı: 1, 42 - 49, 31.01.2026
https://doi.org/10.47482/acmr.1645687

Öz

Amaç: Fitomoleküller, antioksidan ve anti-inflamatuar etkileri sayesinde nörodejeneratif hastalıkları iyileştirebilir. Bu çalışmanın amacı, fitoöstrojenik bir ajan olan daidzeinin, pentilentetrazol (PTZ) kaynaklı nöbet modelinde nöbet şiddeti ve oksidatif stres üzerindeki etkisini değerlendirmektir.
Yöntem: Erkek farelere intraperitoneal olarak daidzein (1 ve 5 mg/kg) enjekte edildi ve 30 dakika sonra tek bir konvülsif doz PTZ uygulandı. Gruplar şu şekildeydi: PTZ Kontrol, PTZ+Diazepam, PTZ+Daidzein 1 mg/kg, PTZ+Daidzein 5 mg/kg ve PTZ+DMSO. Nöbet başlangıcı ve nöbet evreleri, Racine sınıflandırmasına göre 30 dakikalık bir gözlem süresi boyunca puanlandı. Serum örnekleri, otomatik kolorimetrik bir yöntem kullanılarak oksidatif stres parametrelerini değerlendirmek için toplandı.
Bulgular:Daidzeinin 1 mg/kg dozunda (ilk nöbet sunumu ve modifiye evre p=0.001) uygulanması, 5 mg/kg uygulanması hariç, diazepam ile benzer şekilde nöbet oluşumunu engelledi. Daidzeinin her iki dozu da (1 ve 5 mg/kg) serum antioksidan parametrelerini (total tiyol (p=0.425), nahiv tiyol (p=0.350)) artırmadı.
Sonuçlar: Diazepam ile karşılaştırıldığında düşük dozda daidzeinin, oksidatif stres parametrelerinde daha az artışa neden olup nöbetleri önleyebilmesi, daidzeinin potansiyel antikonvülsan bir ajan olabileceğini düşündürmektedir.

Proje Numarası

1919B012105107

Kaynakça

  • Dichter MA. The epilepsies and convulsive disorders. In: Isselbacher KJ, editor. Harrison’s Principles of Internal Medicine. New York: McGraw-Hill; 1994. p.2223–33.
  • Shen B, Shi Y, Fu Y, Cao Y, Wang Y, Fang J. Deep brain stimulation on cognition in epilepsy: A concentration on learning and memory. Brain Res Bull. 2024;219:111134.
  • Fisher RS. Animal models of the epilepsies. Brain Res Brain Res Rev. 1989;14(3):245-78.
  • Löscher W, Schmidt D. Strategies in antiepileptic drug development: is rational drug design superior to random screening and structural variation? Epilepsy Res. 1994;17(2):95-134.
  • Chung YH, Kim WK, Ko KH, Bach JH, Ko KH, Bach JH, et al. Role of oxidative stress in epileptic seizures. Neurochem Int. 2011;59(2):122–37.
  • Menon B, Ramalingam K, Kumar RV. Oxidative stress in patients with epilepsy is independent of antiepileptic drugs. Seizure. 2012;21(10):780–784.
  • Perrone S, Negro S, Tataranno ML, Buonocore G. Oxidative stress and antioxidant strategies in newborns. J Matern Fetal Neonate. 2010;23(Suppl 3):63–65.
  • Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014;47(18):326–332.
  • Matteucci E, Giampietro O. Thiol signalling network with an eye to diabetes. Molecules. 2010;15(12):8890–8903.
  • Prabhu A, Sarcar B, Kahali S, Yuan Z, Johnson JJ, Adam KP, et al. Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma growth. Cancer Res. 2014;74(3):787–796.
  • Sumien N, Cunningham JT, Davis DL, Engelland R, Fadeyibi O, Farmer GE, et al. Neurodegenerative Disease: Roles for Sex, Hormones, and Oxidative Stress. Endocrinol. 2021;162(11):bqab185.
  • Teleanu DM, Niculescu AG, Lungu II, Radu CI, Vladâcenco O, Roza E, et al. An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. Int J Mol Sci. 2022;23(11):5938.
  • Sharma D, Singh V, Kumar A, Singh TG. Genistein: A promising ally in combating neurodegenerative disorders. Eur J Pharmacol. 2025;991:177273.
  • Ahmed T, Javed S, Tariq A, Budzynska B, D’Onorrio G, Daglia M, et al. Daidzein and its effects on Brain. Curr Med Chem. 2016;24(4):365-375.
  • Aras AB, Guven M, Akman T, Ozkan A, Sen HM, Duz U, et al. Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats. Neural Regen Res. 2015;10(1):146-152.
  • Wei J, Yang F, Gong C, Shi X, Wang G. Protective effect of daidzein against streptozotocin-induced Alzheimer's disease via improving cognitive dysfunction and oxidative stress in rat model. J Biochem Mol Toxicol. 2019;33(6):e22319.
  • Ariyani W, Koibuchi N. The effect of soy isoflavones in brain development: the emerging role of multiple signaling pathways and future perspectives. Endocr J. 2024;71(4):317-333.
  • Öğün MN, Çetinkaya A, Beyazçiçek E. The effect of vortioxetine on penicillin-induced epileptiform activity in rats. SciELO Arq Neuro-Psiquiatr. 2019;77(6):412-417.
  • Racine RJ, Gartner JG, Burnham WM. Epileptiform activity and neural plasticity in limbic structures. Brain Res. 1972;47(1):262-8.
  • Parida S, Singh TU, Thangamalai R, Narasimha Reddy ChE, Panigrahi M, Kandasamy K, et al. Daidzein pretreatment improves survival in mouse model of sepsis. J Surg Res. 2015;197(2):363-73.
  • Kim JW, Jin YC, Kim YM, Rhie S, Kim HJ, Seo HG, et al. Daidzein administration in vivo reduces myocardial injury in a rat ischemia/reperfusion model by inhibiting NF-kappaB activation. Life Sci. 2009;84(7-8):227-34.
  • Křížová L, Dadáková K, Kašparovská J, Kašparovský T. Isoflavones. Molecules. 2019;24:1076.
  • Zaheer K, Humayoun Akhtar M. An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. Crit Rev Food Sci Nutr. 2017;57(6):1280-1293.
  • Mahdy HM, Mohamed MR, Emam MA, Karim AM, Abdel-Naim AB, Khalifa AE. Puerarin ameliorates 3-nitropropionic acid-induced neurotoxicity in rats: possible neuromodulation and antioxidant mechanisms. Neurochem Res. 2014;39(2):321-32.
  • Gong G, Ganesan K, Wan Y, Liu Y, Huang Y, Luo Y, et al. Unveiling the neuroprotective properties of isoflavones: current evidence, molecular mechanisms and future perspectives. Crit Rev Food Sci Nutr. 2024;24:1-37.
  • Hu QP, Yan HX, Peng F, Feng W, Chen FF, Huang XY, et al. Genistein protects epilepsy-induced brain injury through regulating the JAK2/STAT3 and Keap1/Nrf2 signaling pathways in developing rats. Eur J Pharmacol. 2021;912:174620.
  • El-Sayed RM, Fawzy MN, Zaki HF, Abd El-Haleim EA. Neuroprotection impact of biochanin A against pentylenetetrazol-kindled mice: Targeting NLRP3 inflammasome/TXNIP pathway and autophagy modulation. Int Immunopharmacol. 2023;115:109711.
  • Kalandakanond-Thongsong S, Daendee S, Thongsong B, Srikiatkhachorn A. Daidzein, but not genistein, has anxiolytic-like effect on intact male Wistar rats. Behav Brain Res. 2024;474:115172.
  • Westmark CJ, Westmark PR, Malter JS. Soy-based diet exacerbates seizures in mouse models of neurological disease. J Alzheimers Dis. 2013;33(3):797-805.
  • Rodriguez-Gomez A, Filice F, Gotti S, Panzica G. Perinatal exposure to genistein affects normal development of anxiety and aggressive behaviors and nitric oxide system in CD1 male mice. Physiol Behav. 2014;133:107-14.
  • Wisniewski AB, Cernetich A, Gearhart JP, Klein SL. Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice. Physiol Behav. 2005;84(2):327-34.
  • Rangel-Galván M, Rangel A, Romero-Méndez C, Dávila EM, Castro ME, Caballero NA, et al. Inhibitory Mechanism of the Isoflavone Derivative Genistein in the Human CaV3.3 Channel. ACS Chem Neurosci. 2021;12(4):651-659.
  • Laddha AP, Kulkarni YA. Daidzein ameliorates peripheral neuropathy in Sprague Dawley rats. Front Pharmacol. 2024;15:1385419.
  • Haider T, Khan S, Bibi T, Zahra SA, Ali H, Din FU, et al. Daidzein ameliorates experimental traumatic brain injury-induced neurological symptoms by suppressing oxidative stress and apoptosis. J Biochem Mol Toxicol. 2024;38(11):e70019.
  • Pang D, Yang C, Luo Q, Li C, Liu W, Li L, et al. Soy isoflavones improve oxidative stress induced hypothalamic inflammation and apoptosis in high fat diet-induced obese male mice through PGC1-alpha pathway. Aging (Albany NY). 2020;12(9):8710-8727.
  • Jin Y, Wu H, Cohen EM, Wei J, Jin H, Prentice H, et al. Genistein and daidzein induce neurotoxicity at high concentrations in primary rat neuronal cultures. J Biomed Sci. 2007;14(2):275-84.
  • Celec P, Hodosy J, Pálffy R, Gardlík R, Halčák L, Ostatníková D. The short-term effects of soybean intake on oxidative and carbonyl stress in men and women. Molecules. 2013;18(5):5190-200.

Daidzein Inhibits Pentylenetetrazol-Induced Seizures in Mice

Yıl 2026, Cilt: 7 Sayı: 1, 42 - 49, 31.01.2026
https://doi.org/10.47482/acmr.1645687

Öz

Background: Phytomolecules, through their antioxidant and anti-inflammatory effects, can improve neurodegenerative diseases. The aim of this study was to evaluate the effect of daidzein, a phytoestrogenic agent, on seizure severity and oxidative stress in a pentylenetetrazol (PTZ)-induced seizure model.
Methods: Male mice were injected intraperitoneally (i.p.) with daidzein (1 and 5 mg/kg) and, 30 minutes later, a single convulsive dose of PTZ was administered. The groups were as follows: PTZ Control, PTZ+Diazepam, PTZ+Daidzein 1 mg/kg, PTZ+Daidzein 5 mg/kg, and PTZ+DMSO. Seizure onset and seizure stages were scored over a 30-minute observation period according to the Racine classification. Serum samples were collected to evaluate oxidative stress parameters using an automated colorimetric method.
Results: Administration of daidzein at a dose of 1 mg/kg (first seizure presentation and modified stage p=0.001), but not 5 mg/kg, inhibited seizure formation similarly to diazepam. Neither dose of daidzein (1 and 5 mg/kg) increased serum antioxidant parameters (total thiol (p=0.425), native thiol(p=0.350)).
Conclusion: Low-dose daidzein can prevent seizure while causing a smaller increase in oxidative stress parameters compared to diazepam suggests that it may have potential as an anticonvulsant agent.

Destekleyen Kurum

TÜBİTAK 2209

Proje Numarası

1919B012105107

Kaynakça

  • Dichter MA. The epilepsies and convulsive disorders. In: Isselbacher KJ, editor. Harrison’s Principles of Internal Medicine. New York: McGraw-Hill; 1994. p.2223–33.
  • Shen B, Shi Y, Fu Y, Cao Y, Wang Y, Fang J. Deep brain stimulation on cognition in epilepsy: A concentration on learning and memory. Brain Res Bull. 2024;219:111134.
  • Fisher RS. Animal models of the epilepsies. Brain Res Brain Res Rev. 1989;14(3):245-78.
  • Löscher W, Schmidt D. Strategies in antiepileptic drug development: is rational drug design superior to random screening and structural variation? Epilepsy Res. 1994;17(2):95-134.
  • Chung YH, Kim WK, Ko KH, Bach JH, Ko KH, Bach JH, et al. Role of oxidative stress in epileptic seizures. Neurochem Int. 2011;59(2):122–37.
  • Menon B, Ramalingam K, Kumar RV. Oxidative stress in patients with epilepsy is independent of antiepileptic drugs. Seizure. 2012;21(10):780–784.
  • Perrone S, Negro S, Tataranno ML, Buonocore G. Oxidative stress and antioxidant strategies in newborns. J Matern Fetal Neonate. 2010;23(Suppl 3):63–65.
  • Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014;47(18):326–332.
  • Matteucci E, Giampietro O. Thiol signalling network with an eye to diabetes. Molecules. 2010;15(12):8890–8903.
  • Prabhu A, Sarcar B, Kahali S, Yuan Z, Johnson JJ, Adam KP, et al. Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma growth. Cancer Res. 2014;74(3):787–796.
  • Sumien N, Cunningham JT, Davis DL, Engelland R, Fadeyibi O, Farmer GE, et al. Neurodegenerative Disease: Roles for Sex, Hormones, and Oxidative Stress. Endocrinol. 2021;162(11):bqab185.
  • Teleanu DM, Niculescu AG, Lungu II, Radu CI, Vladâcenco O, Roza E, et al. An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. Int J Mol Sci. 2022;23(11):5938.
  • Sharma D, Singh V, Kumar A, Singh TG. Genistein: A promising ally in combating neurodegenerative disorders. Eur J Pharmacol. 2025;991:177273.
  • Ahmed T, Javed S, Tariq A, Budzynska B, D’Onorrio G, Daglia M, et al. Daidzein and its effects on Brain. Curr Med Chem. 2016;24(4):365-375.
  • Aras AB, Guven M, Akman T, Ozkan A, Sen HM, Duz U, et al. Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats. Neural Regen Res. 2015;10(1):146-152.
  • Wei J, Yang F, Gong C, Shi X, Wang G. Protective effect of daidzein against streptozotocin-induced Alzheimer's disease via improving cognitive dysfunction and oxidative stress in rat model. J Biochem Mol Toxicol. 2019;33(6):e22319.
  • Ariyani W, Koibuchi N. The effect of soy isoflavones in brain development: the emerging role of multiple signaling pathways and future perspectives. Endocr J. 2024;71(4):317-333.
  • Öğün MN, Çetinkaya A, Beyazçiçek E. The effect of vortioxetine on penicillin-induced epileptiform activity in rats. SciELO Arq Neuro-Psiquiatr. 2019;77(6):412-417.
  • Racine RJ, Gartner JG, Burnham WM. Epileptiform activity and neural plasticity in limbic structures. Brain Res. 1972;47(1):262-8.
  • Parida S, Singh TU, Thangamalai R, Narasimha Reddy ChE, Panigrahi M, Kandasamy K, et al. Daidzein pretreatment improves survival in mouse model of sepsis. J Surg Res. 2015;197(2):363-73.
  • Kim JW, Jin YC, Kim YM, Rhie S, Kim HJ, Seo HG, et al. Daidzein administration in vivo reduces myocardial injury in a rat ischemia/reperfusion model by inhibiting NF-kappaB activation. Life Sci. 2009;84(7-8):227-34.
  • Křížová L, Dadáková K, Kašparovská J, Kašparovský T. Isoflavones. Molecules. 2019;24:1076.
  • Zaheer K, Humayoun Akhtar M. An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. Crit Rev Food Sci Nutr. 2017;57(6):1280-1293.
  • Mahdy HM, Mohamed MR, Emam MA, Karim AM, Abdel-Naim AB, Khalifa AE. Puerarin ameliorates 3-nitropropionic acid-induced neurotoxicity in rats: possible neuromodulation and antioxidant mechanisms. Neurochem Res. 2014;39(2):321-32.
  • Gong G, Ganesan K, Wan Y, Liu Y, Huang Y, Luo Y, et al. Unveiling the neuroprotective properties of isoflavones: current evidence, molecular mechanisms and future perspectives. Crit Rev Food Sci Nutr. 2024;24:1-37.
  • Hu QP, Yan HX, Peng F, Feng W, Chen FF, Huang XY, et al. Genistein protects epilepsy-induced brain injury through regulating the JAK2/STAT3 and Keap1/Nrf2 signaling pathways in developing rats. Eur J Pharmacol. 2021;912:174620.
  • El-Sayed RM, Fawzy MN, Zaki HF, Abd El-Haleim EA. Neuroprotection impact of biochanin A against pentylenetetrazol-kindled mice: Targeting NLRP3 inflammasome/TXNIP pathway and autophagy modulation. Int Immunopharmacol. 2023;115:109711.
  • Kalandakanond-Thongsong S, Daendee S, Thongsong B, Srikiatkhachorn A. Daidzein, but not genistein, has anxiolytic-like effect on intact male Wistar rats. Behav Brain Res. 2024;474:115172.
  • Westmark CJ, Westmark PR, Malter JS. Soy-based diet exacerbates seizures in mouse models of neurological disease. J Alzheimers Dis. 2013;33(3):797-805.
  • Rodriguez-Gomez A, Filice F, Gotti S, Panzica G. Perinatal exposure to genistein affects normal development of anxiety and aggressive behaviors and nitric oxide system in CD1 male mice. Physiol Behav. 2014;133:107-14.
  • Wisniewski AB, Cernetich A, Gearhart JP, Klein SL. Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice. Physiol Behav. 2005;84(2):327-34.
  • Rangel-Galván M, Rangel A, Romero-Méndez C, Dávila EM, Castro ME, Caballero NA, et al. Inhibitory Mechanism of the Isoflavone Derivative Genistein in the Human CaV3.3 Channel. ACS Chem Neurosci. 2021;12(4):651-659.
  • Laddha AP, Kulkarni YA. Daidzein ameliorates peripheral neuropathy in Sprague Dawley rats. Front Pharmacol. 2024;15:1385419.
  • Haider T, Khan S, Bibi T, Zahra SA, Ali H, Din FU, et al. Daidzein ameliorates experimental traumatic brain injury-induced neurological symptoms by suppressing oxidative stress and apoptosis. J Biochem Mol Toxicol. 2024;38(11):e70019.
  • Pang D, Yang C, Luo Q, Li C, Liu W, Li L, et al. Soy isoflavones improve oxidative stress induced hypothalamic inflammation and apoptosis in high fat diet-induced obese male mice through PGC1-alpha pathway. Aging (Albany NY). 2020;12(9):8710-8727.
  • Jin Y, Wu H, Cohen EM, Wei J, Jin H, Prentice H, et al. Genistein and daidzein induce neurotoxicity at high concentrations in primary rat neuronal cultures. J Biomed Sci. 2007;14(2):275-84.
  • Celec P, Hodosy J, Pálffy R, Gardlík R, Halčák L, Ostatníková D. The short-term effects of soybean intake on oxidative and carbonyl stress in men and women. Molecules. 2013;18(5):5190-200.
Toplam 37 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Metabolik Tıp
Bölüm Araştırma Makalesi
Yazarlar

Hümeyra Çelik 0000-0002-3394-2438

Canan Akünal Türel 0000-0001-8791-235X

Murat Alışık 0000-0003-0434-3206

Cansu Kara Öztabağ 0000-0003-2108-2458

Şule Nur Türk 0009-0007-9797-714X

Proje Numarası 1919B012105107
Gönderilme Tarihi 24 Şubat 2025
Kabul Tarihi 4 Eylül 2025
Yayımlanma Tarihi 31 Ocak 2026
Yayımlandığı Sayı Yıl 2026 Cilt: 7 Sayı: 1

Kaynak Göster

APA Çelik, H., Akünal Türel, C., Alışık, M., … Kara Öztabağ, C. (2026). Daidzein Inhibits Pentylenetetrazol-Induced Seizures in Mice. Archives of Current Medical Research, 7(1), 42-49. https://doi.org/10.47482/acmr.1645687

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