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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (12): 1470-1475.doi: 10.3736/jcim20121221

• Original Experimental Research • Previous Articles     Next Articles

Estrogen-dependent effect of soy extract on pentylenetetrazole-induced seizures in rats

Mohammadpour Toktam1,Hosseini Mahmoud1,2(),Karami Reza2,Reza Sadeghnia Hamid2,Reza Ebrahimzadeh Bideskan Ali3,Enayatfard Lili1   

  1. 1. Neuroscience Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
    2. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
    3. Department of Anatomy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Received:2012-05-30 Accepted:2012-10-15 Online:2012-12-20 Published:2018-12-15

Objective: To study the different effects of soy extract on pentylenetetrazole (PTZ)-induced seizures in the presence and absence of ovarian hormones in rats, and the gender-dependent differences in the effects of phytoestrogens on behavior.
Methods: Male and female Wistar rats were randomly divided into nine groups with eight in each, namely, male-saline (M-saline), male-low-dose soy (M-LDS), male-high-dose soy (M-HDS), sham-saline (Sh-saline), sham-low-dose soy (Sh-LDS), sham-high-dose soy (Sh-HDS), ovariectomized-saline (OVX-saline), ovariectomized-low-dose soy (OVX-LDS) and ovariectomized-high-dose soy (OVX-HDS). The rats of groups 7 to 9 were ovariectomized under ketamine anesthesia. The rats of groups 2, 5 and 8 were treated by 20 mg/kg of soy extract while the animals of groups 3, 6 and 9 received 60 mg/kg of soy extract for two weeks. In groups 1, 4 and 7, saline was injected instead of soy extract. The animals were then injected by a single dose of PTZ (90 mg/kg body weight, intraperitoneally) and placed in a plexiglas cage and the latency to minimal clonic seizure (MCS) and generalized tonic-clonic seizure (GTCS) was recorded.
Results: Both MCS and GTCS latency in M-LDS and M-HDS groups was significantly lower than that in M-saline group (P<0.05 or P<0.01). Treatment for female sham rats by soy extract did not affect MCS and GTCS latency. The animals of OVX-LDS and OVX-HDS groups had lower MCS and GTCS latency in comparison with OVX-saline group (P<0.05 or P<0.01).
Conclusion: It is concluded that the phytoestrogens of soy affect seizure severity induced by PTZ, but their effects are different in the presence or absence of ovarian hormones. However, further studies are necessary to be done.

Key words: soybeans, seizures, ovariectomy, rat


Group n MCS latency GTCS latency
Male-saline 8 62.20±3.26 102.36±11.14
Sham-saline 8 45.06±2.00** 68.73±1.81**
OVX-saline 8 45.30±1.86** 85.20±3.21*△


Group n MCS latency GTCS latency
Male-saline 8 62.20±3.26 102.36±11.14
Male-LDS 8 44.60±1.88** 81.40±5.22*
Male-HDS 8 34.20±1.81**▲ 72.00±2.22**


Group n MCS latency GTCS latency
OVX-saline 8 45.30±1.86 85.20±3.21
OVX-LDS 8 34.90±0.70□□ 69.90±4.36
OVX-HDS 8 24.30±1.86□□■■ 67.80±3.05□□
[1] Mackedanz V, Mattos CB, Feksa LR, Wannmacher CM, Wyse AT . Ovariectomy alters energy metabolism in rat striatum: effect of supplementation with soy diet rich in isoflavones. Metab Brain Dis. 2011 ; 26(2) : 97-105.
doi: 10.1007/s11011-010-9216-8
[2] Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA . Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology. 1998; 139(10) : 4252-4256.
doi: 10.1210/endo.139.10.6216
[3] Kurzer MS, Xu X . Dietary phytoestrogens. Annu Rev Nutr. 1997; 17:353-381.
doi: 10.1146/annurev.nutr.17.1.353
[4] Mäkelä SI, Pylkkänen LH, Santti RS, Adlercreutz H . Dietary soybean may be antiestrogenic in male mice.J Nutr. 1995; 125(3) : 437-445.
doi: 10.1093/jn/125.3.437 pmid: 7876918
[5] Mäkelä SI, Santti R, Salo L, McLachlan JA . Phytoestrogens are partial estrogen agonists in the adult male mouse. Environ Health Perspect. 1995; 103(Suppl 7) : 123-127.
doi: 10.2307/3432520 pmid: 421
[6] Pan Y, Anthony M, Watson S, Clarkson TB . Soy phytoestrogens improve radial arm maze performance in ovariectomized retired breeder rats and do not attenuate benefits of 17β-estradiol treatment. Menopause. 2000 ; 7(4) : 230-235.
doi: 10.1097/00042192-200007040-00004
[7] Duffy R, Wiseman H, File SE . Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones. Pharmacol Biochem Behav. 2003; 75(3) : 721-729.
doi: 10.1016/S0091-3057(03)00116-3
[8] File SE, Jarrett N, Fluck E, Duffy R, Casey K, Wiseman H . Eating soya improves human memory. Psychopharmacology (Berl). 2001; 157(4):430-436.
doi: 10.1007/s002130100845 pmid: 11605103
[9] Adlercreutz H, Mazur W . Phyto-oestrogens and Western diseases. Ann Med. 1997; 29(2):95-120.
doi: 10.3109/07853899709113696
[10] Ebrahimzadeh Bideskan AR, Hosseini M, Mohammadpour T, Karami R, Khodamoradi M, Nemati Karimooy H, Alavi H . Effects of soy extract on pentylenetetrazol- induced seizures in ovariectomized rats. J Chin Integr Med. 2011; 9(6):611-618. English with abstract inChinese.
doi: 10.3736/jcim20110606
Ebrahimzadeh Bideskan AR, Hosseini M, Mohammadpour T, Karami R, Khodamoradi M, Nemati Karimooy H, Alavi H. 大豆提取物抗戊四唑所致卵巢切除大鼠痉挛的作用.中西医结合学报. 2011; 9(6):611-618.
doi: 10.3736/jcim20110606
[11] Kishida T, Mizushige T, Ohtsu Y, Ishikawa S, Nagamoto M, Izumi T, Obata A, Ebihara K . Dietary soy isoflavone- aglycone lowers food intake in female rats with and without ovariectomy. Obesity (Silver Spring) . 2008; 16(2):290-297.
doi: 10.1038/oby.2007.68 pmid: 18239635
[12] Lund TD, West TW, Tian LY, Bu LH, Simmons DL, Setchell KD, Adlercreutz H, Lephart ED . Visual spatial memory is enhanced in female rats (but inhibited in males) by dietary soy phytoestrogens. BMC Neurosci. 2001 ; 2:20.
doi: 10.1186/1471-2202-2-20
[13] Saffarzadeh F, Eslamizade MJ, Nemati Karimooy HA, Hadjzadeh MA, Khazaei M, Hosseini M . The effect of L-arginine on Morris water maze tasks of ovariectomized rats. Acta Physiol Hung. 2010; 97(2):216-223.
doi: 10.1556/APhysiol.97.2010.2.8 pmid: 20511131
[14] Hosseini M, Sharifi MR, Alaei H, Shafei MN, Karimooy HA . Effects of angiotensin II and captopril on rewarding properties of morphine. Indian J Exp Biol. 2007 ; 45(9):770-777.
pmid: 17907742
[15] Hosseini M, Sadeghnia HR, Salehabadi S, Alavi H, Gorji A . The effect of L-arginine and L-NAME on pen- tylenetetrazole induced seizures in ovariectomized rats,in vivo study. Seizure. 2009; 18(10):695-698.
doi: 10.1016/j.seizure.2009.09.008
[16] Hosseini M, Ghasemzadeh Rahbardar M, Sadeghnia HR, Rakhshandeh H . Effects of different extracts of Rosa damascena on pentylenetetrazol-induced seizures in mice. J Chin Integr Med. 2011; 9(10):1118-1124. English with abstract inChinese.
Hosseini M, Ghasemzadeh Rahbardar M, Sadeghnia HR, Rakhshandeh H. 突厥蔷薇提取物抗戊四唑所致小鼠痉挛的作用.中西医结合学报. 2011; 9(10):1118-1124.
[17] Rakhshandah H, Hosseini M . Potentiation of pentobarbital hypnosis by Rosa damascena in mice. Indian J Exp Biol. 2006; 44(11) : 910-912.
[18] Arai Y, Sekine Y, Murakami S . Estrogen and apoptosis in the developing sexually dimorphic preoptic area in female rats. Neurosci Res. 1996; 25(4):403-407.
doi: 10.1016/0168-0102(96)01070-X pmid: 8866522
[19] Foldvary-Schaefer N, Falcone T . Catamenial epilepsy: pathophysiology, diagnosis, and management. Neurology. 2003; 61(6 Suppl 2) : S2-S15.
doi: 10.1212/WNL.61.6_suppl_2.S2 pmid: 14504304
[20] Finn DA, Gee KW . The estrus cycle, sensitivity to convul- sants and the anticonvulsant effect of a neuroactive steroid.J Pharmacol Exp Ther. 1994; 271(1):164-170.
[21] Snyder-Keller A, Sam C, Keller RW Jr . Enhanced susceptibility to cocaine- and pentylenetetrazol-induced seizures in prenatally cocaine-treated rats. Neurotoxicol Teratol. 2000; 22(2) : 231-236.
doi: 10.1016/S0892-0362(99)00061-6
[22] Mejias-Aponte CA, Jimenez-Rivera CA, Segarra AC . Sex differences in models of temporal lobe epilepsy : role of testosterone. Brain Res. 2002; 944(1-2):210-218.
doi: 10.1016/S0006-8993(02)02691-4 pmid: 12106683
[23] Kitani K, Sato Y, Kanai S, Nokubo M, Ohta M, Masuda Y . Age related increased threshold for electroshock seizure in BDF1 mice. Life Sci. 1985; 36(7):657-662.
doi: 10.1016/0024-3205(85)90170-5 pmid: 3968982
[24] Bujas M, Pericic D, Jazvinscak M . Influence of gender and gonadectomy on bicuculline-induced convulsions and on GABAa receptors. Brain Res Bull. 1997; 43(4):411-416.
doi: 10.1016/S0361-9230(97)00027-0 pmid: 9241444
[25] Edwards HE, Burnham WM, Mendonca A, Bowlby DA, MacLusky NJ . Steroid hormones affect limbic afterdischarge thresholds and kindling rates in adult female rats. Brain Res. 1999; 838(1-2):136-150.
doi: 10.1016/S0006-8993(99)01619-4
[26] Hoffman GE, Moore N, Fiskum G, Murphy AZ . Ovarian steroid modulation of seizure severity and hippocampal cell death after kainic acid treatment. Exp Neurol. 2003; 182:124-134.
doi: 10.1016/S0014-4886(03)00104-3
[27] Pereira M Jr, Soares JM Jr, Valente SG, Oliveira PB, Cavalheiro EA, Amado D, Baracat EC . Estrogen effects on pilocarpine-induced temporal lobe epilepsy in rats. Maturitas. 2009; 62(2) : 190-196.
doi: 10.1016/j.maturitas.2008.10.014 pmid: 19111409
[28] Czlonkowska AI, Krzascik P, Sienkiewicz-Jarosz H, Siemiatkowski M, Szyndler J, Bidzinski A, Ptaznik A . The effects of neurosteroids on picrotoxin-, bicuculline- and NMDA-induced seizures, and a hypnotic effect of ethanol. Pharmacol Biochem Behav. 2000; 67(2):345-353.
doi: 10.1016/S0091-3057(00)00369-5
[29] Balduzzi R, Cupello A, Robello M . Modulation of the expression of GABAa receptors in rat cerebellar granule cells by protein tyrosine kinases and protein kinase C. Biochim Biophys Acta. 2002; 1564(1):263-270.
doi: 10.1016/S0005-2736(02)00460-1
[30] Murphy DD, Cole NB, Greenberger V, Segal M . Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons.J Neurosci. 1998; 18(7) : 2550-2559.
[31] Hosseini M, Taiarani Z, Hadjzadeh MA, Salehabadi S, Tehranipour M, Alaei HA . Different responses of nitric oxide synthase inhibition on morphine-induced antinociception in male and female rats. Pathophysiology. 2011 ; 18(2) : 143-149.
doi: 10.1016/j.pathophys.2010.05.004
[32] McEwen BS . Invited review: Estrogens effects on the brain: multiple sites and molecular mechanisms.J Appl Physiol. 2001; 91(6):2785-2801.
doi: 10.1080/10407780590945579 pmid: 11717247
[33] Linford NJ, Dorsa DM . 17β-Estradiol and the phytoestrogen genistein attenuate neuronal apoptosis induced by the endoplasmic reticulum calcium-ATPase inhibitor thapsigargin. Steroids. 2002; 67(13-14):1029-1040.
doi: 10.1016/S0039-128X(02)00062-4
[34] Schreihofer DA, Do KD, Schreihofer AM . High-soy diet decreases infarct size after permanent middle cerebral artery occlusion in female rats. Am J Physiol Regul Integr Comp Physiol. 2005; 289(1):R103-R108.
[35] Lovekamp-Swan T, Glendenning ML, Schreihofer DA . A high soy diet enhances neurotropin receptor and Bcl- XL gene expression in the brains of ovariectomized female rats. Brain Res. 2007; 1159:54-66.
doi: 10.1016/j.brainres.2007.05.026
[36] Grisar T . Glial and neuronal Na +-K + pump in epilepsy . Ann Neurol. 1984; 16(Suppl) : S128-S134.
doi: 10.1002/ana.410160719 pmid: 6095737
[37] Chen JQ, Contreras RG, Wang R, Fernandez SV, Shoshani L, Russo IH, Cereijido M, Russo J . Sodium/ potassium ATPase (Na + , K +-ATPase) and ouabain/ related cardiac glycosides : A new paradigm for development of anti-breast cancer drugs? Breast Cancer Res Treat. 2006; 96(1) : 1-15.
[38] Zhou W, Cunningham KA, Thomas ML . Estrogen regulation of gene expression in the brain: a possible mechanism altering the response to psychostimulants in female rats. Brain Res Mol Brain Res. 2002; 100(1-2):75-83.
doi: 10.1016/S0169-328X(02)00134-1
[39] Nogowski L, Mackowiak P, Kandulska K, Szkudelski T, Nowak KW . Genistein-induced changes in lipid metabolism of ovariectomized rats. Ann Nutr Metab. 1998; 42(6):360-366.
doi: 10.1159/000012756 pmid: 9895424
[40] Kirkman LM, Lampe JW, Campbell DR, Martini MC, Slavin JL . Urinary lignan and isoflavonoid excretion in men and women consuming vegetable and soy diets. Nutr Cancer. 1995; 24(1):1-12.
doi: 10.1080/01635589509514388 pmid: 7491293
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