SIÇANLARDA SİMVASTATİN UYGULAMASI İLE OLUŞAN ANKSİYOJENİK-BENZERİ DAVRANIŞTA NİTRİK OKSİTİN ETKİSİ

Yıl 2020, Cilt: 22 Sayı: 2, 180 - 191, 31.08.2020

Mehmet Alkanat , Hafize Özdemir , Şükrücan Baytan

https://doi.org/10.24938/kutfd.651692

Öz

Amaç: 3-hidroksi-3-metil-glutaril-koenzim A redüktaz enzimini inhibe ederek kolesterol sentezini engelleyen statinler tüm dünyada hiperlipidemilerin tedavisinde yaygın olarak kullanılmaktadır. Statin ailesinin önemli bir üyesi olan simvastatinin, çeşitli çalışmalarda nitrik oksit miktarını arttırdığı gösterilmiştir. Bu çalışmada, simvastatin kullanımına bağlı olarak değişen anksiyete seviyesine, nitrik oksit düzeyinin etki edip etmediği araştırıldı.

Gereç ve Yöntemler: Sprague-Dawley cinsi sıçanlardan, her grupta 8 denek olmak üzere, 7 grupta deneklerin anksiyete düzeyinin gözlenmesi için yükseltilmiş artı labirent ve açık alan testi uygulandı. Çözücü grubuna fosfat tamponlu çözelti uygulanırken, yalnızca simvastatin alan gruba 20 ve 40 mg/kg dozda simvastatin uygulandı. Diğer iki gruptaki deneklere 20 mg/kg simvastatine ek olarak 10 mg/kg L-NAME, diğer gruba ise 50mg/kg L-NAME uygulandı. Kalan son iki gruba 40 mg/kg simvastatin ile 10 ve 50 mg/kg L-NAME dozları uygulandı. Çözücü ve ilaç uygulamasının 1, 4, 7, 10, 15, 21 ve 28. günlerinde tüm gruplar test edildi. Yükseltilmiş artı labirent kapalı kolda kalma süresi ve açık alan testi marjin zamanları ölçüldü. Sıçanlara uygulanan çeşitli simvastatin ve L-NAME dozlarının, yükseltilmiş artı labirent ve açık alan testine etkisi, iki yönlü varyans analizi kullanılarak değerlendirildi.

Bulgular: Yükseltilmiş artı labirent testinde sadece simvastatin 40 mg/kg grubunun çözücü grubuna göre kapalı kol kalma süresinin anlamlı olarak arttırdığını gösterdi (p<0.05). Ayrıca açık alan testinde simvastatin 20 ve 40 mg/kg grubu çözücü grubuna göre marjin süresini anlamlı olarak arttırdı (p<0.05). 10 ve 50 mg/kg L-NAME dozları simvastatinin yarattığı etkiyi ortadan kaldırdı. Bulgularda gözlenen kapalı kolda kalma zamanının ve marjin süresinin artışı anksiyojenik benzeri davranış olarak değerlendirilmiştir.

Sonuç: Bulgular simvastatin uygulaması ile oluşan anksiyojenik-benzeri davranışın L-NAME etkisiyle engellendiğini, dolayısıyla simvastatin uygulamasıyla oluşan anksiyojenik-benzeri davranışın nitrik oksit mekanizmasıyla düzenlendiğini göstermektedir.

Anahtar Kelimeler

Statinler, Simvastatin, anksiyete, Nitrik oksit, yükseltilmiş artı labirent, açık alan

Teşekkür

Çalışmadan sonra aramızdan ayrılan Sn. Doç. Dr. Şükrücan Hasan BAYTAN’ı saygıyla anıyor ve rahmet diliyoruz.

Effect of Nitric Oxide on Anxiogenic-like Behavior Induced by Simvastatin Administration in Rats

Öz

Objective: Statins which inhibit cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase enzymes are used widely for treatment of hyperlipidemia. In this study, altered anxiety levels by simvastatin use have been investigated to assess whether these effects are caused by changed nitric oxide levels.

Material and Methods: Seven groups of animals each consisting of 8 Sprague Dawley rats were tested by elevated plus maze and open field methods, to observe anxiety levels. The vehicle group was administered phosphate buffered saline alone while two of simvastatin groups were administered 20 or 40 mg/kg simvastatin and vehicle. Another two groups of animals were both administered 20 mg/kg simvastatin with vehicle. When one of these groups was additionally administered 10 mg/kg L-NAME, the other group was given 50 mg/kg L-NAME along with simvastatin. Remaining two groups were both given 10 and 50 mg/kg L-NAME doses along with 40 mg/kg simvastatin. All groups were tested in the 1st, 4th, 7th, 10th, 15th, 21st and 28th days of vehicle or drug administration. The research was analyzed using two way analyzes of variances.

Results: In the elevated plus maze test, simvastatin alone showed that the 40 mg / kg group significantly increased the closed arm time compared to the solvent group (p<0.05). Moreover, in the open field test, simvastatin 20 and 40 mg / kg groups significantly increased the margin duration compared to the solvent group (p<0.05). Doses of 10 and 50 mg/kg L-NAME abolished the effect created by simvastatin. The increase in closed arm time and margin time observed in the findings was evaluated as anxiogenic-like behavior.

Conclusion: The findings show that the anxiogenic-like behavior caused by the administration of simvastatin is prevented by the effect of L-NAME, thus the anxiogenic-like behavior caused by the administration of simvastatin is regulated by the nitric oxide mechanism.

Anahtar Kelimeler

statins, simvastatin, anxiety, nitric oxide, elevated plus maze, open field

Kaynakça

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