Necmiye CANACANKATAN, Mehmet SATAR, Kenan DAĞLIOĞLU, Erdal TAŞKIN, Kenan ÖZCAN

Allopürinolün hipoksik-iskemik beyin hasarı oluşturulan yenidoğan sıçanlarda kaspaz-3 ve kaspaz-8 aktivitesi üzerine etkisi

Amaç: Hipoksi-iskemi sonrası reperfüzyon-reoksijenasyon döneminde küçük damar endotel hücrelerinde serbest radikallerin üretimine neden olan siklooksijenaz ve ksantin oksidazın aktive olduğu iki önemli yol tetiklenir. Ksantin oksidaz inhibitörü olan allopürinolün hipoksik iskemik ansefalopatide nöroprotektif olabileceği gösterilmiştir. Kaspaz-3 ve kaspaz-8 nöronal apopitozda anahtar bir role sahiptir. Bu çalışmada yenidoğan sıçanlara hipoksi-iskemi sonrası değişik dozlarda uygulana allopürinolün beyin dokusunda apopitozun öncül proteinleri olan kaspaz-3 ve kaspaz- 8 aktivitesine etkisi araştırıldı. Gereç ve Yöntem: Çalışmada her gruba yedi günlük 10 sıçan alındı. Etik Kurul onayı (TIBDAM-25) alınan sıçanların sol karotis arteri bağlanıp 2,5 saat hipokside bırakıldı. Kontrol (S) ve hipoksi iskemi (H-İ) gruplarına ilaveten, bir gruba (AL48) 30 dak ve 12 saat sonra, bir gruba da (AL72) 30 dak ve 12 saate ilaveten 24 saat sonra 24 mg/kg dozda allopurinol periton içine uygulandı. Son ilaç uygulanmasından 24 saat sonra sıçanlar kafaları kesilerek beyin dokusunda kaspaz-3 ve kaspaz 8 aktivitelerine bakıldı. Bulgular: Tüm grupların kendi sağ ve sol beyin kaspaz-3 ve kaspaz-8 aktiviteleri arasında fark yoktu (p>0,05). H-İ, AL48 ve AL72 gruplarının her iki beyin küresindeki kaspaz-3 ve kaspaz-8 düzeyleri kontrol grubuna göre belirgin yüksekti (hepsi için p=0,0001). Ancak AL48 grubu ile H-İ grubu arasındaki kaspaz düzeyleri farklılık göstermez iken (p>0,05), AL72 grubunda kaspaz düzeyleri hem Hİ hem de AL48 grubuna göre daha düşüktü (sırası ile p=0,0001, p=0,001). Çıkarımlar: Toplam 72 mg/kg allopürinol verilen hipoksik iskemik yenidoğan sıçanların beyin dokularında kaspaz-3 ve kaspaz-8 düzeylerinin azalması, bu dozdaki allopürinolün hipoksik iskemik hasarda nöronal apopitozu azaltarak etkili olabileceğini düşündürmektedir. (Türk Ped Arfl 2013; 48: 48-52)

Allopurinol s effect on caspase-3 and caspase-8 activity in hypoxic-ischemic newborn rats

Aim: During reperfusion period of hypoxia-ischemia, cyclooxygenase and xanthine oxidase pathways are induced. A xanthine oxidase inhibitor, allopurinol has been shown to be neuroprotective in hypoxic- ischemic encephalopathy. Caspase-8 and caspase-3 have a key role in neuronal apoptosis. We aimed to test repeated doses of allopurinol s effect on caspase-3 and caspase-8 activities in newborn rats with hypoxic-ischemic encephalopathy. Material and Method: Seven days old newborn rats were taken and there were 10 rats in each group. After Ethical Committee was approved (TIBDAM-25), rats were subjected to left carotid artery ligation and hypoxia (8% oxygen and 92% nitrogen) for two and half hours. Hypoxic ischemic rats treated with 24 mg/kg allopurinol 30 minutes and 12 hours (AL48 group), and 30 minutes, 12 and 24 hours (AL72 group) after hypoxic- ischemic insult. Twenty four hours after last dose, rats were decapitated. The others groups were sham and saline- treated hypoxic- ischemic (H-I) group. Caspase- 3 and caspase- 8 activities were measured in both hemispheres. Results: There was no difference in caspase-3 and caspase-8 activities between right and left brain hemispheres in each group (p>0.05). Caspase-3 and caspase-8 activities were significantly lower in sham group when compared to H-I group, AL48 and AL72 groups (all ofp=0.0001). Even though there were no difference activities of caspase- 3 and caspase- 8 between H-I group and AL48 group (p>0.05), activities of caspase- 3 and caspase- 8 in AL72 group were significantly lower than H-I group and AL48 group (respectively p= 0.0001, p=0.001). Conclusions: Decreased activities of caspase- 3 and caspase- 8 in AL72 group may suggest that totally dosage of 72 mg/kg allopurinol may be effective for reducing neuronal apoptosis in newborn rats with hypoxic- ischemic insult. (Turk Arch Ped 2013; 48: 48-52)

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