MUHAMMED ENES ALTUĞ, M. İsmet MELEK, Suat ERDOĞAN, VESİLE DÜZGÜNER, Atakan ÖZTÜRK, ALTUĞ KÜÇÜKGÜL

The neuroprotective effect of caffeic acid phenethyl ester on global ischemia-reperfusion injury in rat brains

Bu çalışma iskemi-reperfüzyon (I/R) hasarlı rat beyinlerinde fosfodiesteraz 4 (PDE4) mRNA izoenzimleri, oksidant ve antioksidant savunma sistemi üzerine kafeik asit fenetil ester (KAFE)in nöroprotektif etkilerini araştırmak amacıyla yapıldı. Yirmi bir adet rat rastgele üç eşit gruba ayrıldı. Sham-kontrol, iskemi/reperfüzyon (I/R) ve I/R+KAFE. Sham-kontrol grubundaki ratlara bilateral common carotid arter oklüzyonu yapılmaksızın sadece cerrahi müdahalede bulunuldu. İskemi/reperfüzyon (I/R) bilateral common carotid arterlerin atravmatik klempler ile 30 dakika oklüzyonu ve takiben arter klempleri açılarak reperfüzyonu ile sağlandı. I/R+KAFE grubu I/R grubu ile aynı cerrahi usüle tabi tutuldu fakat oklüzyondan 1 saat önce ve reperfüzyondan 12 saat sonra iki defa 15 µmol kg -1 dozunda intraperitoneal KAFE verildi. Ratlar iskemi/ reperfüzyondan 24 saat sonra sakrifiye edildi. Beyin korteksindeki cAMP düzeyi ELISA ile, PDE4 mRNA izoenzim transkripsiyonları ise qRT-PCR ile değerlendirildi. KAFE iskemi ile uyarılan beyin korteksindeki NO üretimini önemli oranda azalttı. I/R grubu ile karşılaştırıldığında SOD, CAT ve XO aktivitelerini KAFE anlamlı düzeyde değiştirmezken, GSH-Px aktivitesini önemli oranda arttırdı. KAFE cAMP düzeyini değiştirmeksizin PDE4A ve PDE4B düzeyini önemli oranda azalttı. İskemi ile uyarılan nörolojik hasar skorları KAFE tarafından azaltıldı. Bu sonuçlar KAFEnin global beyin iskemi/reperfüzyon hasarı sırasında rat beyinlerinde antioksidant savunma sistemini ve NO salınımını hafifce dengelediğini önerir. Ayrıca KAFE bazı PDE4 izoenzim düzeylerini azaltarak nöroprotektif etki sağlar.

Rat beyinlerinde global iskemi-reperfüzyon hasarı üzerine kafeik asit fenetil esterin nöroprotektif etkisi

The aim of this study was to investigate the neuroprotective efects of cafeic acid phenethyl ester (CAPE) on phosphodiesterase 4 (PDE4) mRNA isoenzymes, oxidant and antioxidant defence in ischemia/reperfusion (I/R) injured rat brains. Twenty-one rats were randomly divided into three equal groups: sham-control, ischemia/reperfusion (I/R) and I/R+CAPE. Rats in sham-control group underwent only surgical intervention without bilateral common carotid artery occlusion. Ischemia/reperfusion was induced by bilateral common carotid artery occlusion with atraumatic clips for 30 min, followed by artery reopening. The I/R+CAPE group was subjected to the same surgical procedure as I/R group, but CAPE was administered intraperitoneally at the dose of 15 µmol kg -1 twice, 1 h before occlusion and at 12 th h of reperfusion. The rats were sacrificed 24 h after I/R. The cAMP concentration was analyzed by ELISA and PDE4 isozyme mRNA transcriptions were evaluated by qRT-PCR methodology in the brain cortex. Ischemia-induced NO production was significantly attenuated by CAPE in the cerebral cortex. CAPE significantly enhanced GSH-Px activity, while SOD, CAT and XO activities non-significantly changed, as compared to the I/R group. CAPE significantly decreased PDE4A and PDE4B transcripts, without changing cAMP levels compared to I/R group. Ischemia-induced neurologic deficit scores were reduced by CAPE. These results suggest that CAPE slightly modulates the antioxidant defense system and NO release in rat brain during global cerebral ischemia/reperfusion injury. In addition, CAPE treatments produce the neuroprotective efect by reducing the levels of some PDE4 transcriptions.

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