Faruk ERDEN, Güner ULAK, Esin GÖLDELİ, Nejat GACAR

Farelerde Pentilentetrazol ve Striknin ile Oluşturulan Konvülsiyonlar Üzerinde 7-Nitro İndazolün Etkisi

Amaç: Nitrik oksidin (NO) santral fizyolojik olaylarda, hücrereler arası bir haberci olarak rolü olduğuna dair çeşitli kanıtlar mevcuttur. Çeşitli deneysel konvülsiyon modellerinde nitrik oksid etkisiz, prokonvülsan veya antikonvülsan olarak bildirilmektedir. Bu çalışmada beyindeki nitrik oksid sentaz (NOS) tipine spesifik bir inhibitor olan 7-nitro indazolün (7-Nj), striknin (ST) ve pentilentetrazol (PIZ) konvülsiyonları üzerindeki etkisini araştırmayı planladık. Yöntem: Subkütan (SK) ı.5 mg/kg ST veya 85 mg/kg PTZ verilerek; ilk miyoklonik spazm (jMS), toplam konvülsiyon süresi, ölüm zamanı ve ölüm oranları saptandı. 7 Nİ, AO veya serum fizyolojik (0. 1 ml/ 25gr) ST veya PTZ uygulamasından 30 dk önce intraperitoneal olarak uygulandı. 7-Nİ intraperitoneal (i.p.) kullanım için yerfıstığı yağıında (arachis oil, AO; peanut oil) çözüldü. Bulgular: 7-Ni (30 mg/kg) her iki tip konvülsiyon modelindeki tüm parametreler üzerinde etkisiz bulundu. Ancak AO ve SF alan fareler karşılaştırıldığında AO, ST gruplarında tüm parametreleri, PTZ gruplarında ise sadece İMS'ı anlamlı olarak uzattı (p < 0,05). Sonuç: Bu sonuç muhtemelen i.p. verilen yerfıstığı yağının, daha sonra SK. verilen ST ve PTZ 'ün absorpsiyon ve/veya dağılım özelliklerini etkilemiş olabileceğini akla getirmektedir. Sonuç olarak çalışmamızda kullanılan doz ve doz aralığında, 7-Nİ bu tip konvülsiyonlar üzerinde etkisiz görülmektedir.

Anahtar Kelimeler:

Nitrik oksid, 7-nitro indazol, striknin, pentilentetrazol

The Effect of 7-Nitro Indazole on Strychnine and Pentylenetetrazole-Induced Seizures in Mice

Objective: There are some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in the central physiological mechanisms. It is suggested that NO might be anticonvulsant, proconvulsant or ineffective on seizure activity in various experimental seizure models. In this study, the effects of 7-nitro indazole (7-NI), a selective inhibitor for the form of nitric oxide synthase enzyme found in the brain, on strychnine (ST) and pentylenetetrazole (PTZ) induced seizures in mice were investigated. Methods: ST (1.5 mg/kg) or PTZ (85 mg/kg) were administered subcutaneously (s.c.) to produce seizures. 7-NI, vehicle or saline (0. ı ml/25g, i.p.) were given 30 minutes prior to ST or PTZ to separate mice groups. 7-NI(30mg/kg) was dissolved in arachis oil (AO; peanut oil) for intraperitoneal (i.p.) administration. Results: The first myoclonic jerk (FMJ), the total convulsion time (TCT), the survival time, and the rate of mortality was recorded. 7-NI had no effect on all parameters, both in ST and PıZ induced seizures. Interestingly AO compared to saline controls significantly delayed FMJ and survival time; increased TCT; decreased the rate of mortality induced by ST (p < 0.05). AO also significantly delayed FMJ induced by PTZ compared to saline controls. Conclusion: It is very possible that the i.p. injection of AO could have altered absorption and/or distribution of the subsequent s.c. injection of ST or PTZ. These observations suggested that 7-NI, at dose and time intervals used in this study, had no effect on seizure activity.

Keywords:

nitric oxide, 7-nitro indazole, strychinine, pentylenetetrazole,

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