Levent ÖZDOĞAN, Taner AYERDEN, Dilşen ÖRNEK, Handan ŞAŞTIM, Oya KILCI, Canan ÜN, Bayazıt DİKMEN

The neurotoxic effect of intrathecal diclofenac sodium in rats

Amacımız intratekal diklofenak sodyumun tek ve tekrarlayan uygulanmasının olası nörotoksik etkisinin araştırılmasıdır. Çalışmamız 24 adet 250-300 gr ağırlığında erkek Spraque Dawley cinsi ratta gerçekleştirilmiştir. Dört saatlik açlık süresi sonrasında, 100 mg kg-1 ketamin hidroklorür ve 10 mg kg-1 ksilazin hidroklorür intraperitoneal uygulanarak anestezi sağlanan ratlar randomize olarak üç gruba ayrıldı. Grup 2 (n=8)’deki ratlar 7. günde intratekal 10 μl (200 μg) diklofenak sodyum, Grup 1 (n=8)’e intratekal 10 μl %0.9’luk serum fizyolojik ve Grup 3 (n=8)’e intratekal 10 μl (200 μg) diklofenak sodyum her gün intratekal girişim 7 olacak şekilde lomber bölgeden 0.40x50 mm’lik iğne ile intratekal uygulama yapıldı. Çalışma süresince klinik nörotoksisite açısından hayvanlar incelendi. %10’luk formaldehid enjekte edilerek dokuların fiksasyonu sağlandıktan sonra medulla spinalisleri eksplore edildi ve histopatolojik olarak elektron mikroskobu ile değerlendirildi. İstatistiksel değerlendirmede Kruskal Wallis testi kullanıldı. P

Anahtar Kelimeler:

sıçan, elektron mikroskopisi, sinir hücresi, sinir toksisitesi, toksisite

Ratlarda intratekal diklofenak sodyumun nörotoksik etkisi

We aimed to investigate the possible neurotoxic eff ects of single and repeated doses of diclofenac sodium administered to rats. The current study included 24 male Sprague-Dawley rats weighing 250-300 g. At the end of a 4-h fasting period, the rats were randomly split into 3 groups following the establishment of anesthesia with intraperitoneal delivery of 100 mg kg-1 of ketamine hydrochloride and 10 mg kg-1 of xylazine chloride. Group 2 (n=8) received 10 μl (200 μg) of intrathecal diclofenac sodium on 7th day as a single dose, whereas the rats in group 1 (n=8) and group 3 (n=8) were received 10 μl of intrathecal 0.9% saline and 10 μl (200 μg) of intrathecal diclofenac sodium via a 0.40 x 50 mm needle per day for 7 days. During the course of the study the animals were examined with regard to clinical toxicity. After fixating the tissues by injection of 10% formaldehyde, spinal cords were explored and evaluated histopathologically with electron microscopy. Statistical analysis was performed with the Kruskal Wallis test. P values <0.05 were considered statistically significant. While electron microscopic examination showed no changes in the control group, diclofenac sodium exhibited neurotoxic eff ects that were more marked following the 7-days treatment. Diclofenac sodium was neurodegenerative, depending on the dose, and cellular organelles were observed to have compression associated with extracellular edema. Neurodegeneration was thought to be occured with a significant reduction in cellular activity.

Keywords:

rats, electron microscopy, neurons, neurotoxicity, toxicity,

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