High dosage of agmatine alleviates pentylenetetrazole‑induced chronic seizures in rats possibly by exerting an anticonvulsive effect

Xu,Huiqin; Ou,Fuyong; Wang,Pei; Naren,Mangdula; Tu,Dongpei; Zheng,Rongyuan

doi:10.3892/etm.2014.1711

July-2014 Volume 8 Issue 1

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July-2014 Volume 8 Issue 1

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Article

High dosage of agmatine alleviates pentylenetetrazole‑induced chronic seizures in rats possibly by exerting an anticonvulsive effect

Authors:
- Huiqin Xu
- Fuyong Ou
- Pei Wang
- Mangdula Naren
- Dongpei Tu
- Rongyuan Zheng
View Affiliations / Copyright

Affiliations: Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Department of Neurology, Chenzhou No. 1 People's Hospital, Chenzhou, Hunan 423000, P.R. China
Pages: 73-78
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Published online on: May 14, 2014

https://doi.org/10.3892/etm.2014.1711
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Abstract

The aim of the present study was to investigate the mechanism underlying the effects of different doses of agmatine in rats with chronic epilepsy. To generate chronic epilepsy models, rats pretreated with different doses of agmatine (20, 40 and 80 mg/kg) were intraperitoneally injected with pentylenetetrazole (35 mg/kg) for 28 consecutive days. Epileptic behavior was observed using behavioral measurements of convulsion for 1 h after each treatment with pentylenetetrazole. Morphological alterations of the hippocampal neurons were also observed using hematoxylin and eosin staining. In addition, the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus were detected by immunohistochemistry. Furthermore, reverse transcription polymerase chain reaction was performed to detect the mRNA expression of two subunits (NR1 and NR2B) of the N‑methyl‑D‑aspartic acid (NMDA) receptor in the rat hippocampus. The results demonstrated that administration of agmatine (80 mg/kg) significantly decreased the daily average grade of epileptic seizures and also reduced neuronal loss and astrocyte hyperplasia in the hippocampal area. Furthermore, agmatine (80 mg/kg) affected the mRNA expression levels of the NR1 subunit of the NMDA receptor, however, agmatine had no effect on the expression of iNOS in the hippocampus. Higher doses of agmatine inhibited the effect of pentylenetetrazole in rats, reduced astrocytic hyperplasia and neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Our results suggest that agmatine has an anticonvulsive effect in chronic epilepsy.

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1	Raasch W, Schäfer U, Chun J and Dominiak P: Biological significance of agmatine, an endogenous ligand at imidazoline binding sites. Br J Pharmacol. 133:755–780. 2001. View Article : Google Scholar : PubMed/NCBI
2	Demehri S, Homayoun H, Honar H, et al: Agmatine exerts anticonvulsant effect in mice: modulation by α2-adrenoceptors and nitric oxide. Neuropharmacology. 45:534–542. 2003.
3	Su RB, Wei XL, Zheng JQ, Liu Y, Lu XQ and Li J: Anticonvulsive effect of agmatine in mice. Pharmacol Biochem Behav. 77:345–349. 2004. View Article : Google Scholar : PubMed/NCBI
4	Feng Y, LeBlanc MH and Regunathan S: Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: a potential mechanism for the anticonvulsive effects. Neurosci Lett. 390:129–133. 2005. View Article : Google Scholar
5	Luszczki JJ, Czernecki R, Wojtal K, Borowicz KK and Czuczwar SJ: Agmatine enhances the anticonvulsant action of Phenobarbital and valproate in the mouse maximal electroshock seizure model. J Neural Transm. 115:1485–1494. 2008. View Article : Google Scholar : PubMed/NCBI
6	Bahremand A, Ziai P, Khodadad TK, Payandemehr B, et al: Agmatine enhances the anticonvulsant effect of lithium chloride on pentylenetetrazole-induced seizures in mice: Involvement of L-arginine/nitricoxide pathway. Epilepsy Behav. 18:186–192. 2010. View Article : Google Scholar : PubMed/NCBI
7	Obay BD, Taşdemir E, Tümer C, Bilgin H and Atmaca M: Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides. 29:448–455. 2008. View Article : Google Scholar : PubMed/NCBI
8	Fathollahi Y, Motamedi F, Semnanian S and Zardoshti M: Examination of persistent effects of repeated administration of pentylenetetrazol on rat hippocampal CA1: evidence from in vitro study on hippocampal slices. Brain Res. 758:92–98. 1997. View Article : Google Scholar : PubMed/NCBI
9	Wang XS, Chen YY, Shang XF, et al: Idazoxan attenuates spinal cord injury by enhanced astrocytic activation and reduced microglial activation in rat experimental autoimmune encephalomyelitis. Brain Res. 1253:198–209. 2009. View Article : Google Scholar
10	Stringer JL: Repeated seizures increase GFAP and vimentin in the hippocampus. Brain Res. 717:147–153. 1996. View Article : Google Scholar : PubMed/NCBI
11	Ravizza T, Gagliardi B, Noé F, Boer K, Aronica E and Vezzani A: Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy. Neurobiol Dis. 29:142–160. 2008. View Article : Google Scholar : PubMed/NCBI
12	Ekonomou A and Angelatou F: Upregulation of NMDA receptors in hippocampus and cortex in the pentylenetetrazol-induced ‘kindling’ model of epilepsy. Neurochem Res. 24:1515–1522. 1999.PubMed/NCBI
13	Bengzon J, Kokaia Z, Elmér E, Nanobashvili A, Kokaia M and Lindvall O: Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures. Proc Natl Acad Sci USA. 94:10432–10437. 1997. View Article : Google Scholar : PubMed/NCBI
14	Oses JP, Leke R, Portela LV, et al: Biochemical brain markers and purinergic parameters in rat CSF after seizure induced by pentylenetetrazol. Brain Res Bull. 64:237–242. 2004. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

High dosage of agmatine alleviates pentylenetetrazole‑induced chronic seizures in rats possibly by exerting an anticonvulsive effect

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