Attenuation of Liver Ischemia/Reperfusion Induced Apoptosis by Epigallocatechin-3-Gallate Via Down-Regulation of NF-κB and c-Jun Expression

Introduction Hepatic ischemia/reperfusion (I/R) activates Kupffer cells and initiates severe oxidative stress with enhanced production of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-α). ROS and TNF-α mediate the expression of nuclear factors and kinases, activating the signal transduction pathway, and triggering apoptosis. The aim of our study was to evaluate the potential protective effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-κB, c-Jun, and caspase-3 in a model of severe hepatic I/R. Materials and Methods Thirty Wistar rats were allocated into three groups. Sham operation, I/R, and I/R-EGCG 50 mg/kg. Hepatic ischemia was induced for 60 min by Pringle's maneuver. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, scanning electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry for NF-κB, c-Jun, caspase-3, analysis on liver specimens and aspartate (AST), and alanine (ALT) transferases analysis in serum, were performed 120 min after reperfusion. Results Apoptosis as indicated by TUNEL and caspase-3 was widely expressed in the I/R group but very limited in the EGCG treated group. Liver was stained positive for NF-κB and c-Jun in the I/R group but failed to be stained positive in the EGCG treated group. MDA, MPO, AST, and ALT showed marked increase in the I/R group and significant decrease in EGCG treated group. Significant alterations of liver specimens were observed by light histology and transmission electron microscopy whilst pretreatment with EGCG resulted in parenchymal preservation. Conclusions Administration of EGCG is likely to inhibit I/R-induced apoptosis and protect liver by down-regulating NF-κB and c-Jun signal transduction pathways.