MK-801 Verilen Ratlarm Cerebellumun'da Makromolekiiler Oksidasyon ve Cape'nin Koruyucu Etkisi

Year 2006, Volume: 7 Issue: 3, - , 01.12.2006

Birsen Ozyurt Huseyin Ozyurt Fatih Ekici Hasan Erdogan Mustafa Sarsılmaz

Abstract

Keywords

-

MK-801 Verilen Ratlarm Cerebellumun'da Makromolekiiler Oksidasyon ve Cape'nin Koruyucu Etkisi

Abstract

Bu çalışmanın amacı MK-801 ile oluşan nörotoksisitede oksidatif stresin etkisini incelemek, oksidatif stresin önlenmesi ile prognozun düzelebileceğinin gösterilmesidir. MK-801 en nörotoksik NMDA reseptör antagonistlerinden biridir. Wistar Albino ratlar 3 gruba ayrıldı: l.grup: Kontrol, 2. grup: MK-80:l, 3. grup: MK— 801+CAPE. MK-80] beş gün intraperitoneal verildi. Tedavi grubuna MK—80l ’e maruzken CAPE verildi. Kontrol grubuna aynı sürede serum fizyolojik intraperitoneal verildi. 7 gün sonra ratlar dekapitasyonla öldürüldü. Serebellumları biyokimyasal analizler için çıkarıldı. Oksidatif stres parametresi olan Nitrik oksit (NO) yanı sıra Malondialdehit (MDA) ve Protein karbonil (PC) seviyeleri kontrol ile karşılaştırıldığında MK-801 grubu serebellumunda anlamlı artmıştı. CAPE ile tedavi edilen grupta NO, MDA ve PC seviyesi MK-80l grubu ile karşılaştırıldıgında ise anlamlı azaldı. Bu çalışmanın sonuçları serebellumda MK-801 ile oluşan nörotoksisitenin patogenesizinde oksidatif stresin önemli rolü olduğunu ortaya koydu. Bu deneysel çalışma aynı zamanda MK-80] ile oluşan nörotoksisite üzerine CAPE’nin koruyucu etkisi olabileceği yönünde bazı deliller sağlar

Keywords

MK—801, CAPE, MDA, PC, NO

References

• Olney JW, Newcomer JW, Farber NB. NMDA
• receptor hypofunction model of schizophrenia. J
• Psychiatr Res, 1999; 33:523-33.
• Javitt DC, Zukin SR. Recent advances in the
• phencyclidine model of schizophrenia. Am J
• Psychiatry, 1991; [48:1301-8.
• Corso TD, Sesma MA, Tenkova TI, Der TC,
• Wozniak DF, Farber NB, Olney JW. Multifocal brain
• damage induced by phencyclidine is augmented by
• pilocarpine. Brain Res, 1997; 75221-14.
• Haring R, Pellegrini-Giampietro DE, Zukin SR,
• Zukin RS, Scheideler MA. High efŞciency
• reconstitution of a phencyclidine/MK-801 receptor
• binding site solubilized from rat forebrain
• membranes. Mol Pharmacol. 1991; 402666-73.
• Ferrer-Montiel AV, Sun W, Montal M. Molecular
• design of the N—methyl-D-aspartate receptor binding
• site for phencyclidine and dizolcipine. Proc Natl
• Acad Sci U S A. 1995; 92:8021-5.
• Hoffman DC. Typical and atypical neuroleptics
• antagonize MK-801-induced locomotion and
• stereotypy in rats. J Neural Transm Gen Sect. 1992;89:1-10.
• Andine P, Widerrnark N, Axelsson R et al..
• Characterization of MK-SOl-induced behavior as a
• putative rat model of pschosis. JPET. 1999;290: 1393-1408.
• Mastropaolo J, Rosse RB, Deutsch Sl. Anabasine, a
• selective nicotinic acetylcholine receptor agonist,
• antagonizes MK-801-elicited mouse popping
• behavior, an animal model of schizophrenia. Behav
• Brain Res. 2004. 31; 53z419-22.
• Deutsch SI, Rosse RB, Billingslea EN, Bellack AS,
• Mastropaolo J. Modulation of MK-801-elicited
• mouse popping behavior by galantamine is complex
• and dose-dependent. Life Sci. 2003. 7318:2355-61. . Rung JP, Carlsson A, Ryden Markinhuhta K,
• Carlsson ML. (+)-MK—801 induced social withdrawal
• in rats; a model for negative symptoms of
• schizophrenia. Prog Neuropsychopharmacol Biol
• Psychiatry. 2005. 29:827-32. . Nakki R, Sharp F., Sagar SM. FOS expression in the
• brainstem and cerebellum following phencyclidine
• and MK801. J Neurosci Res. 1996; 43:203-12.
• Cortas, N. K., Wakid, N. W.:Determination of
• inorganic nitrate in serum and urine by a kinetic
• cadmium-reduction method. Clin Chem
• ;36:1440-1443. . Esterbauer H, Cheeseman KH. Determination of
• aldehydic lipid peroxidation products:
• Malonaldehyde and 4-hydroxynonenal. ln Methods in
• MK-801 Verilen Rat/arm Cerebellumun 'da Makromolekiiler Oksidasyon ve Cape ’nin Koruyucu Etkisi / 67 The Macromoleculer Oxıdation in Cerebellum of Rat Exposed To NIK-80] and The Protective Effect of Cape
• EnzymolOgy, V 186, Oxygen radicals in biological
• systems edited by Packer L, Glazer AN. Academic
• Press, California, 1990, pp 407—421. . Packer L, Glazer NA. Determination of Carbonyl
• Content in Oxidatively ModiŞed Proteins, Methods in
• Enzymology. California. 1990;186:464-479. . Lowry O, Rosenbraugh N, Farr L, Rondall R. Protein
• measurement with the folin-phenol reagent. J Biol
• Chem 1951;183:265-275. . Mahadik SP, Evans D, Lal H. Oxidative stress and ro—
• le of antioxidant and omega-3 essential fatty acid
• supplementation in schizophrenia. Prog
• Neuropsychopharmacol Biol Psychiatry. 2001; 25: 463-93. . Mahadik SP, Mukherjee S, Scheffer R, Correnti EE,
• Mahadik JS. Elevated plasma lipid peroxides at the
• onset of nonaffective psychosis. Biol Psychiatry.
• ; 43:674-9. .Mates JM, Perez-Gomez C, De Castro IN.
• Antioxidant enzymes and human diseases. Clin.
• Biocehmistry. 1999; 32: 595—603. . Akyol O, Herken H, Uz E, Fadillioglu E, Unal S,
• Sogut S, Ozyurt H, Savas HA. The indices of
• endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance. Prog
• Neuropsychopharmacol Biol Psychiatry. 2002; 262995-1005. . Ozyurt B, Sarsilmaz M, Akpolat N, Ozyurt H, Akyol
• O, Herken H, Kus I. The protective effects of omega
• fatty acids against MK-801—induced neurotoxicity
• in prefrontal cortex of rat. Neurochem Int. 2007; 50:196-202. . Herken H, Uz E, Ozyurt H, Akyol 0. Red blood cell
• nitric oxide levels in patients with schizophrenia.
• Schizophr Res. 2001; 52:289-90. . Özyurt B, Güleç M, Özyurt H, Ekici F, Atış Ö, Akbaş
• A. The effect of antioxidant caffeic acid phenethyl es
• ter (CAPE) on some enzyme activities in cisplatin
• induced neurotoxicity in rats. Eur J Gen Med. 2006; 3:167-172. .Sud'ina GF, Mirzoeva OK, Pushkareva MA,
• Korshunova GA, Sumbatyan NV, Varfolomeev SD.
• Caffeic acid phenethyl ester as a lipoxygenase
• inhibitor with antioxidant properties. FEBS Lett. 1993; 329:21-24.
• Kocatepe Tıp Dergisi, Cil 7 No: 3, Eylül 2006.