Effects of Carvedilol on liver ischemia-reperfusion injury in rats

BACKGROUND: The aim of this study was to analyze the potential protective effect of Carvedilol against liver ischemia-reperfusion (I/R) injury in rats.
METHODS: A total of 40 Wistar albino rats were randomly divided into four groups (n=10 each). Group I (Sham/Control group) underwent only laparotomy, Group II (Carvedilol group) was administered carvedilol and then underwent laparotomy, Group III (I/R group) underwent laparotomy and hepatic ischemia/reperfusion, and Group IV (I/R + Carvedilol group) was administered carvedilol and then underwent laparotomy and hepatic ischemia/reperfusion. Blood samples were collected for malondialdehyde, glutathione (GSH), and myeloperoxidase (MPO) analysis. Liver sections were obtained for histopathological analysis and stained with hematoxy-lin-eosin. Tumor necrosis factor-α (TNF-α) and Caspase-3 primary antibodies were used for the immunohistochemical analysis.
RESULTS: Serum GSH levels increased in the I/R + Carvedilol group. MPO activity was increased significantly in the IR group. In I/R + Carvedilol group, serum MPO levels were similar to the control group. Histopathological findings showed reduced dilatation and congestion in vena centralis, regenerative changes in hepatocyte cells with the protected nucleus structure in the I/R + Carvedilol group. Hepatocyte nuclei with increased pycnosis and apoptosis and the dilated vena centralis were observed in I/R group. In the control group, TNF-α showed a positive reaction in macrophage cells around vena centralis. An increase in TNF-α expression was observed in hepatocyte cells of I/R group. Positive expression of caspase-3 in hepatocyte cells and a small number of endothelial and Kupffer cells were seen in I/R group. However, negative caspase-3 expression was seen in hepatocyte, endothelial, and Kupffer cells in I/R + Carvedilol group.
CONCLUSION: Carvedilol may prevent initiation of oxidative stress process, inflammation induction and apoptotic progression.

Karvedilol’ün sýçanlarda karaciðer iskemi-reperfüzyon hasarý üzerine etkileri

AMAÇ: Bu çalýþmanýn amacý, karvedilol’ün sýçanlarda karaciðer iskemi-reperfüzyon (I/R) hasarýna karþý potansiyel koruyucu etkisini analiz etmektir. GEREÇ VE YÖNTEM: Toplam 40 Wistar albino sýçan rastgele dört gruba ayrýldý (her biri n=10). Grup I’e (Sham/Kontrol grubu) sadece laparotomi, Grup II’ye (Karvedilol grubu) karvedilol uygulandý ve ardýndan laparotomi yapýldý, Grup III’e (I/R grubu) laparotomi uygulandý ve hepatik iskemi/reperfüzyon yapýldý ve Grup IV’e (I/R+Karvedilol grubuna) karvedilol uygulandý ve ardýndan laparotomi ve hepatik iskemi/reperfüzyon yapýldý. Ma-londialdehyde (MDA), glutatyon (GSH) and miyeloperoksidaz (MPO) analizi için kan örnekleri toplandý. Histopatolojik analiz için karaciðer kesitleri alýndý ve hematoksilen-eozin ile boyandý. Ýmmünohistokimyasal analiz için tümör nekroz faktor-α (TNF-α) ve kaspaz-3 primer antikorlarý kullanýldý. BULGULAR: Serum GSH seviyeleri I/R+Karvedilol grubunda arttý. IR grubunda MPO aktivitesi önemli ölçüde artmýþtýr. I/R+Karvedilol grubunda serum MPO seviyeleri kontrol grubuna benzerdi. Histopatolojik bulgular, vena centralis’te azalmýþ dilatasyon ve týkanýklýk, I/R+Karvedilol grubunda korunmuþ çekirdek yapýsý ile hepatosit hücrelerinde rejeneratif deðiþiklikler gösterdi. I/R grubunda artmýþ piknoz ve apoptozlu hepatosit çekir-dekleri ve dilate vena centralis izlendi. Kontrol grubunda TNF-α, vena centralis çevresindeki makrofaj hücrelerinde pozitif reaksiyon gösterdi. I/R grubu hepatosit hücrelerinde TNF-α ekspresyonunda artýþ gözlendi. Hepatosit hücrelerinde Kaspaz-3’ün pozitif ekspresyonu ve I/R grubunda az sayýda endotel ve Kupffer hücre görüldü. Ancak I/R+Karvedilol grubunda hepatosit, endotelyal, kupffer hücrelerinde negatif Kaspaz-3 ekspresyonu görüldü.
TARTIÞMA: Karvedilol oksidatif stres sürecinin baþlamasýný, enflamasyon indüksiyonunu ve apoptotik ilerlemeyi önleyebilir.