Sebahattin KARABULUT, Ahmet Şevki TAŞKIRAN

Ursodeoksikolik Asit’in Farelerde Pentilentetrazol ile Oluşturulan Akut Epileptik Nöbetler Üzerine Etkisinin Araştırılması

Öz: Bu çalışmanın amacı, Ursodeksikolik asit (UDKA) ön tedavisinin PTZ ile indüklenen akut epilepsi fare modelinde nöbet davranışına ve hipokampal total oksidan status (TOS) ve kaspaz-3 ekpresyonlarına etkisini araştırmaktır. Çalışmada BALB-c türü 24 hayvan rastgele 4 gruba ayrıldı: Kontrol grubu, PTZ; PTZ ile nöbet indüklenen grup, UDKA-100; 5 gün boyunca UDKA 100 mg kg-1 verilen ve PTZ uygulanan grup, UDKA-200; 5 gün boyunca UDKA 200 mg kg-1 verilen ve PTZ uygulanan grup. UDKA ön tedavisinin nöbet davranışı üzerine istatistiksel olarak anlamlı bir etkisi bulunmadı. UDKA-200 grubunda daha belirgin olmak üzere, UDKA ön tedavisi hipokampal TOS ekspresyonunu anlamlı olarak azalttı. Benzer şekilde, hipokampal kaspaz-3 ekspresyonu UDKA alan gruplarda daha düşük bulundu. Sonuç olarak, UDKA antioksidatif ve antiapoptotik özellikleriyle epilepsi tedavisi için faydalı bir terapotik ajan olabilir.

Anahtar Kelimeler:

Ursodeoksikolik asit, PTZ, Nöbet, Oksidatif Stres

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[1] Fisher RS, van Emde BW, BlumeW, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46:470-72.
[2] Jain S, Webster TJ, Sharma A, Basu B. Intracellular reactive oxidative stress, cell proliferation and apoptosis of Schwann cells on carbon nanofibrous substrates. Biomaterials 2013;34(21):4891-901.
[3] Monte MJ, Marin JJG, Antelo A, Vazquez-Tato J. Bile acids: chemistry, physiology, and pathophysiology. World J Gastroenterol. 2009;15:804-16.
[4] Daruich A, Picard E, Boatright JH, Behar-Cohen F. Review: The bile acids urso- and tauroursodeoxycholic acid as neuroprotective therapies in retinal disease. Mol Vis. 2019; 25:610-24.
[5] Reinicke M, Schröter J, Müller-Klieser D, Helmschrodt C, Ceglarek U. Free oxysterols and bile acids including conjugates - Simultaneous quantification in human plasma and cerebrospinal fluid by liquid chromatography-tandem mass spectrometry. Anal Chim Acta. 2018;1037:245-55.
[6] European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51:237-67.
[7] Amaral JD, Viana RJS, Ramalho RM, Steer CJ, Rodrigues CMP. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res. 2009;50:1721-34.
[8] Bell SM, Barnes K, Clemmens H, et al. Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with Either Sporadic or Familial Alzheimer's Disease. J Mol Biol. 2018;430(21):3942-3953.
[9] Abdelkader NF, Safar MM, Salem HA. Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson’s Disease: Modulation of Mitochondrial Perturbations. Mol Neurobiol. 2016;53:810-17.
[10] Min J-H, Hong Y-H, Sung J-J, Kim S-M, Lee JB, Lee K-W. Oral solubilized ursodeoxycholic acid therapy in amyotrophic lateral sclerosis: a randomized cross-over trial. J Korean Med Sci. 2012;27:200-06.
[11] Racine, RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Neurophysiol. 1972;32:281-94.
[12] Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4): 277-85.
[13] Beit-Yannai E, Kohen R, Horowitz M, Trembovler V, Shohami E. Changes of biological reducing activity in rat brain following closed head injury: A cyclic voltammetry study in normal and heat-acclimated rats. J Cereb Blood Flow & Metab. 1997;17:273-79.
[14] Naziroglu M. Molecular mechanisms of vitamin E on intracellular signaling pathways in brain. In: Goth L, editor. Reactive oxygen species and diseases. Kerala, India: Research Signpost Press; 2007. p. 239-56.
[15] Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH et al. Role of oxidative stress in epileptic seizures. Neurochem Int. 2011;59(2):122-137.
[16] Patsoukis N, Zervoudakis G, Panagopoulos NT, Georgiou CD, Angelatou F, Matsokis NA. Thiol redox state (TRS) and oxidative stress in the mouse hippocampus after pentylenetetrazol-induced epileptic seizure. Neurosci Lett. 2004;357:83-86.
[17] Rodrigues CM, Fan G, Ma X, Kren BT, Steer CJ: A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest. 1998;101:2790-99.
[18] 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;2014:12.
[19] 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;156:431‐43.
[20] Faherty CJ, Xanthoudakis S, Smeyne RJ. Caspase-3–dependent neuronal death in the hippocampus following kainic acid treatment. Mol Brain Res. 1999;70(1):159-63.
[21] Solá S, Amaral JD, Castro RE, Ramalho RM, Borralho PM, Kren BT, et al. Nuclear translocation of UDCA by the glucocorticoid receptor is required to reduce TGF-beta1-induced apoptosis in rat hepatocytes. Hepatology 2005;42:925-34.
[22] Solá S, Castro RE, Kren BT, Steer CJ, Rodrigues CMP. Modulation of nuclear steroid receptors by ursodeoxycholic acid inhibits TGF-beta1-induced E2F-1/p53-mediated apoptosis of rat hepatocytes. Biochem. 2004;43:8429-38.
[23] Naderi M, Jand A, Jand Y, Rahjoo T, Palizvan MR. Effect of ursodeoxycholic acid on pentylenetetrazole kindling and kindling induced memory impairment in rat. J Babol Univ Medical Sci. 2018;20(1):50-56.