Effect of Atorvastatin on Pentylenetetrazol-Induced  Threshold Seizures in Gonadectomized Male Mice

Azizi , S; Heydarieh , N; Jmalu , F

Volume 24, Issue 7 (Oct 2016) JSSU 2016, 24(7): 527-537 | Back to browse issues page

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Azizi S, Heydarieh N, Jmalu F. Effect of Atorvastatin on Pentylenetetrazol-Induced Threshold Seizures in Gonadectomized Male Mice. JSSU 2016; 24 (7) :527-537
URL: http://jssu.ssu.ac.ir/article-1-3565-en.html

Effect of Atorvastatin on Pentylenetetrazol-Induced Threshold Seizures in Gonadectomized Male Mice

S Azizi

, N Heydarieh ^*

, F Jmalu

Abstract: (11254 Views)

Introduction: Epilepsy is a central nervous system disorder that appears as sudden convulsions, and transient, repetitive and unpredictable movement, with sensory-motor and autonomic sources. Statins are a group of blood cholesterol-lowering drugs. According to the results of the anti-inflammatory and vasoprotective effects of statins on cultured brain cells (astrocytes and microglia) and endothelial cells, the purpose of this study was investigating the effect of atorvastatin on pentilentetrazole-induced seizures in gonadectomized male mice.

Methods: 36 male NMRI mice, weighting 30-35 g were used in the study. The mice were divided into two groups (Each group consisted of 18 mice : healthy and gonadectomized groups. The surgical removal of the testicles was gonadectomy and injections were given intraperitoneally. In gonadectomized group, an operation to remove the testicles was done. The DMSO group (0/3 cc) and treatment group were received Atorvastatin (10 mg/kg) intraperitoneally and then 30 minutes after that they received PTZ (80 mg/kg) injection. All injections were administered intraperitoneally. After injection of PTZ- duration of seizure onset (threshold) was recorded. The data were analyzed by one way variance analysis and Tukey’s test using SPSS (p<0. 05).

Results: In healthy group, receiving Atorvastatin significantly increased the time of seizure onset (threshold) compared to solvent DMSO group and on the other hand gonadectomized mice had a significant reduction in the duration of seizures than normal mice (p<0. 001).

Conclusion: The results indicated that the Atorvastatin had anticonvulsant effects and gonadectomy increases seizures.

Keywords: Atorvastatin, Epilepsy, Male Mice, Pentylenetetrazol, Seizure Threshold, Vasectomy

Full-Text [PDF 657 kb] (2160 Downloads)

Type of Study: Original article | Subject: Physiology
Received: 2016/01/12 | Accepted: 2016/09/10 | Published: 2016/10/5

References

1. 1- Jain S. The role of epilepsy management guidelines in a developing country. Neurology Asia. 2011; 16(1): 57-8.

2. 2- Berg AT, Testa FM, Levy SR. Complete remission in nonsyndromic childhood-onset epilepsy. Ann Neurol 2011; 70(40): 566-73.

3. 3- Jackson GD. Classification of the epilepsias2011. Epilepsia 2011; 52(6): 1203-4.

4. 4- Arboix A, Garcia-Eroles L, Oliveres M, Targa C, Balcells M, Massons J. Pretreatment with statins improves early outcome in patients with first-ever ischaemic stroke: a pleiotropic effect of statins or a beneficial effect of hypercholesterolemia? BMC Neurol. 2010; 10(1): 47.

5. 5- An SG, Sohn YT. Crystal forms of atorvastatin. Arch Pharmac Res 2009; 32(6): 933-6.

6. 6- Yan-Wang A, HeChang A, JunZou BC, XinJin B, Zhongquan QI. The effect of atorvastatin on m-RNA levels of inflammatorygenes expressionin human peripheral blood lymphocytes by DNA microarray. Biomed Pharmacother. 2011 Mar; 65(2): 118-22.

7. 7- Qiuting D, Yuejin Y, Lei S, Haiyan Q, Zhimin X. Atorvastatin prevents mesenchymal stem cells from hypoxia and serum-free injury through activating amp-activated protein kinase. Int J Cardiol. 2011; 153(3): 306-11.

8. 8- Rorowski A, Walsh K. Statin therapy and angiogenesis. Curr Opin Lipidol 2003; 14(6): 599-603.

9. 9- Moazzami K, Emamzadeh Fard S, Shabani M. Anticonvulsive effect of atorvastatin on pentylenetetrazole induced seizures in mice: the role of nitric oxide pathway. Fundament Clinic Pharmacol 2013; 27(4): 387-92.

10. 10- Guix FX, Uribesalgo I, Coma M, Muñoz FJ. The physiology and pathophysiology of nitric oxide in the brain. Progress Neurobiol 2005; 76(2): 126-52.

11. 11- Zhao Z, Taylor WD, Styner M, Steffens DC, Krishnan KR, MacFall JR. Hippocampus shape analysis and late-life depression. PLoS One 2008; 3(3): e1837

12. 12- Edinger KL, Frye CA. Testosterones antianxiety and analgesic effect may be due in part to actions of its

13. 5α-reduced metabolites in the hippocampus. Psycho neuroendocrino-logy 2005, 30(5): 418-30.

14. 13- Talebi A, Naghdi N, Sepehri H, Rezayof A. The role of estrogen receptors on spatial learning and memory in CA1 region of adult male rat hippocampus. Iran J Pharm Res 2009; 9(2): 183-91.

15. 14- Balcombe JP. Laboratory environment and rodents’ behavioral needs: a review. Lab Animals 2006; 40: 217-35.

17. 15- Zheng Dongdan, Qing Liang, FanFang Zeng, Zhuocheng Mai, Anping Cai, Ruofeng Qiu, et al. Atorvastatin protects endothelium by decreasing asymmetric dimethylarginine in dyslipidemia rats. Lipids Health Dis 2015; 14(1): 1.

18. 16- Khoshnoud MJ, Tanideh N, Namdarian S. Anticonvulsant activity of atorvastatin against seizure induced by pentylenetetrazole and maximal electroshock in mice. Trend Pharmaceutic Sci 2015; 1(1): 44-7.

19. 17- Sadeghian F, Raei M, Amiri M. Persistent Neck and Shoulder Pains among ComputerOffice Workers: A Longitudinal Study. Arch Hyg Sci 2012; 1(2): 33-40.

20. 18- Lesani A, Javadi-Paydar M, Khodadad TK, Asghari-Roodsari A, Shirkhodaei M, Norouzi A, Dehpour AR. Involvement of the nitric oxide pathway in the anticonvulsant effect of tramadol on pentylenetetrazole-induced seizures in mice. Epilepsy Behav 2010; 19(3): 290-5.

21. 19- Hosseini M, Ghasemzadeh Rahbardar M, Sadeghnia HR and Rakhshandeh H. Effects of different extracts of Rosa damascena on pentylenetetrazol-induced seizures in mice. Zhong Xi Yi Jie He Xue Bao= J Chinese Integra Med 2011; 9(10): 1118-24.

22. 20- Moazzami K, Emamzadeh Fard S, Shabani M. Anticonvulsive effect of atorvastatin on pentylenetetrazole-induced seizures in mice: the role of nitric oxide pathway. Fundam Clin Pharmacol 2013; 27(4): 387-92.

23. 21- Rorowski A, Walsh K. Statin therapy and angiogenesis. Curr Opin Lipidol 2003; 14(6): 599-603.

24. 22- Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005; 45: 89-118.

25. 23- Ito D, Ito O, Mori, Muroya, Cao PY, Takashima K, et al. Atorvastatin upregulates nitric oxide synthases with Rho-kinase inhibition and Akt activation in the kidney of spontaneously hypertensive rats. J Hyperten 2013; 28(11): 2278-88.

26. 24- Hiremath GK, Kotagal P, Bingaman W, Hovinga C, Wyllie E, Morris H, Nelson D. Risk factors for carbamazepine elevation and toxicity following epilepsy surgery. Seizure 2005; 14(5): 312-7.

27. 25- Goldberg AH, Gibaldi M, Kanig JL. Increasing dissolution rates and gastrointestinal absorption of drugs via solid solutions and eutectic mixtures II: Experimental evaluation of a eutectic mixture: Urea-acetaminophen system. working versions of the water maze. Physiol Behav 2008; 93(3): 622-7

28. 26- Shahraki A, Stone TW. Interactions between adenosine and metabotropic glutamate receptors in the rat hippocampal slice. Br J Pharmacol 2003; 138: 1059-68.

29. 27- Kesim Murat, Esin Yulug, Mine Kadioglu, Ilknur Erkoseoglu, Duygun Altintas Aykan. The effect of Simvastatin on Picrotoxin-induced seizure in mice. J Pak Med Assoc. 2012 ;62: 1187-91.

30. 28- Sabogal AM, Arango CA, Cardona GP, Céspedes ÁE. Atorvastatin protects GABAergic and dopaminergic neurons in the nigrostriatal system in an experimental rat model of transient focal cerebral ischemia. Biomédica 2014 ;34(2): 207-17.

31. 29- Ebrahimi A, Schluesener H. Natural polyphenols against neurodegenerative disorders: potentials and pitfalls. Age Res Rev 2012; 11(2): 329-45.

32. 30- Vandresen-Filho S, Martins WC, Bertoldo DB, Mancini G, Herculano BA, de Bem AF, Tasca CI. Atorvastatin prevents cell damage via modulation of oxidative stress, glutamate uptake and glutamine synthetase activity in hippocampal slices subjected to oxygen/glucose deprivation. Neurochem Int 2013; 62(7): 948-55.

33. 31- DING Q, DONG Y, JIN Y, SUI HJ. The mechanisms of neuroprotective effect of atorvastatin on glutamate-induced neurotoxicity in cultured cortical neurons of rats. J Chinese Pharmacol Bulletin 2010; 12: 025.

34. 32- Cardenas-Rodriguez N, Huerta-Gertrudis B, Rivera-Espinosa L, Montesinos-Correa H, Bandala C, Carmona-Aparicio L, et al. Role of oxidative stress in refractory epilepsy: evidence in patients and experimental models. Int J Molecul Sci 2013; 14(1): 1455-76.

35. 33- Chuang YC. Mitochondrial dysfunction and oxidative stress in seizure-induced neuronal cell death. Acta Neurol Taiwan 2010; 19(1): 3-15.

36. 39- Greig D, Alcaino H, Castro PF, Garcia L, Verdejo HE, Navarro M, et al. xanthine– oxidase inhibitors and statins in shronic heart failure: effects on vascular parameters. J Heart Lung Transplant 2011; 30(4): 408-13.

37. 34- Lefer DJ, Scalia R, Jones SP, Sharp BR, Hoffmeyer MR, Farvid AR, et al. HMG-CoA reductase inhibition protects the diabetic myocardium from ischemia-reperfusion injury. FASEB J 2001; 15: 1454-6.

38. 35- Inamoto S, Yoshioka T, Yamashita C, Miyamura M, Mori T, Ukimura A, et al. Pitavastatin reduces oxidative stress and attenuates intermittent hypoxia-induced left ventricular remodeling in lean mice. Hypertens Res 2010; 33(6): 579-86.

39. 36- Scribano MD, Baez MD, Florencia B, Tarán MD, Franco S, Balceda AG, et al. Effects of Atorvastatin on Oxidative Stress Biomarkers and Mitochondrial Morphofunctionality in Hyperfibrinogenemia-Induced Atherogenesis. Adv Med 2014 23; 2014.

40. 37- Kulak WW, Sobaniec K, Wojtal, S Czucwar . Calcium modolation in epilepsy. Pol J Pharmacol 2004; 56(1): 29-41.

41. 38- Bosel J, Gandor F, Harms C, Synowitz M, Harms U, Djoufack PC. Neuroprotective effects of atorvastatin against glutamate- induced excitotoxicity in primary cortical neurones. J Neurochem 2005; 92(6): 1386-98.

42. 39- Shimada T, Takemiya T, Sugiura H, Yamagata K. Role of inflammatory mediators in the pathogenesis of epilepsy. Mediators Inflamma 2014; 2014.

43. 40- Balosso S, Maroso M, Sanchez-Alavez M, Ravizza T, Frasca A, Bartfai T, et al. A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1beta. Brain 2008; 131(Pt 12): 3256-65.

44. 41- Lehtimaki KA, Keranen T, Huhtala H, Hurme M, Ollikainen J, Honkaniemi J, et al. Regulation of IL-6 system in cerebrospinal fluid and serum compartments by seizures: the effect of seizure type and duration. J Neuroimmunol 2004; 152(1-2): 121-5.

45. 42- Foresti ML, Arisi GM, Shapiro LA. Role of glia in epilepsy-associated neuropathology, neuroinflammation and neurogenesis. Brain Res Rev 2010; 66(1-2): 115-22.

46. 43- Dunn SE, Youssef S, Goldstein MJ, Prod'homme T, Weber MS, Zamvil SS, et al. Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin. J Exp Med 2006; 203(2): 401-12.

48. 44- Chow SC. Immunomodulation by statins: mechanisms and potential impact on autoimmune diseases. Arch Immunol Ther Exp (Warsz) 2009; 57(4): 243-51.

49. 45- Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010; 10(3): 170-81.

51. 46- Sun AY, Wang Q, Simonyi A, Sun GY. Botanical phenolics and brain health. Neuromolecular Med 2008; 10(4): 259-74.

52. 47- Miles C, Green R, Hines M. Estrogen treatment effects on cognition, memory and mood in male-to-female transsexuals. Hormones Behav 2006; 50(5): 708-17.

53. 48- Vignes M, Maurice T, Lanté F, Nedjar M, Thethi K, Guiramand J, Récasens M. Anxiolytic properties of green tea polyphenol (−)-epigallocatechin gallate (EGCG). Brain Res 2006; 1110(1): 102-15.