Proanthocyanidin Alleviates Liver Ischemia/Reperfusion Injury by Suppressing Autophagy and Apoptosis via the

Background and Aims:Hepatic ischemia-reperfusion injury(IRI)is a common pathophysiological phenomenon in clinical practice,which usually occurs in liver transplantation,liver resection,severe trauma,and hemorrhagic shock.Proanthocyanidin(PC),exerted from various plants with antioxidant,antitumor,and antiaging activity,were administrated in our study to investigate the underlying mechanism of its protective function on IRI.Methods:Two doses of PC(50 mg/kg,100 mg/kg)were given to BALB/c mice by intragastric administration for 7 days before partial(70%)warm IR surgery.Serum and liver tissues were collected 2,8,and 24 h after reperfusion for relevant experiments.Results:The results of transaminase and hematoxylin and eosin staining indicated that PC pretreatment significantly alleviated IRI in mice.Serum total superoxide dismutase increased and malondialde-hyde decreased in PC pretreatment groups.Enzyme-linked immunosorbent assays,western blotting,quantitative real-time polymerase chain reaction,and immunohistochemistry showed that inflammation,apoptosis,and autophagy in PC preprocessing groups were significantly inhibited and were dose-dependent.The protein,mRNA expression,and immunohistochemical staining results of peroxisome proliferator-activated receptor alpha(PPARa)and peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1a)in the PC pretreatment groups were significantly upregulated compared with the IR group in a dose-dependent manner.Conclusions:PC pretreatment suppressed inflammation,apoptosis,and autophagy via the PPAR-α signaling pathway to protect against IRI of the liver in mice.

NF-kappaB/I-kappaB pathway during ischemia reperfusion injury of rat liver

Objective To determine the role of the NF-kappaB/I-kappaB pathway during ischemia reperfusion (I/R) injury to rat liver. Methords A group of rats underwent partial hepatic ischemia and reperfusion. The left and median lobe of the liver was subjected to ischemia for 90 minutes followed by reperfusion for previously specified periods. NF-kappaB activity was analyzed by electrophoretic mobility shift assay (EMSA). The protein level of I-kappaB was assessed using Western blot analysis. A semiquantitative reverse transcriptase polymerase chain reaction was used to analyze TNF-α and ICAM-1 mRNA levels. Results During liver I/R injury,NF-kappaB activation was induced in a time-dependent fashion. NF-kappaB was activated within 1 hour and 2 hours after the initiation of reperfusion and decreased afer 4 hours. The I-kappaB protein level was decreased in the cytoplasm after 2 hours,and the messenger RNA expression of TNF-α and ICAM-1 were increased simultaneously. Conclusions The data suggest that I-kappaB protein was degraded during hepatic I/R injury,NF kappaB was realeased and bound to special sequence in the promoters of budget genes,which regulated the expression of TNF-α and ICAM-1 mRNA. This provides evidence that the NF-kappaB/I-kappaB pathway plays an important modulating role in the expression of proinflammatory genes relevant to the development of ischemia reperfusion injury.