Attenuation of liver ischemia/reperfusion induced apoptosis by epigallocatechin-3-gallate via down-regulation of NF-kappaB and c-Jun expression.
BACKGROUND
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-alpha). ROS and TNF-alpha 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-kappaB, c-Jun, and caspase-3 in a model of severe hepatic I/R.


METHODS
Thirty Wistar rats were allocated into three groups. Sham operation, I/R, and I/R-EGCG 50mg/kg. Hepatic ischemia was induced for 60min 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-kappaB, c-Jun, caspase-3, analysis on liver specimens and aspartate (AST), and alanine (ALT) transferases analysis in serum, were performed 120min 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-kappaB 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-kappaB and c-Jun signal transduction pathways.
Giakoustidis
Dimitrios E
DE
Department of Transplant Surgery, Medical School, Aristotle University and Hippokration General Hospital, Thessaloniki, Greece. dgiak@auth.gr <dgiak@auth.gr>
Giakoustidis
Alexandros E
AE
Iliadis
Stavros
S
Koliakou
Kokona
K
Antoniadis
Nikolaos
N
Kontos
Nikolaos
N
Papanikolaou
Vasilios
V
Papageorgiou
Georgios
G
Kaldrimidou
Eleni
E
Takoudas
Dimitrios
D
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000473:pathology / Q000601:surgery*; D008107:Liver Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics*; D009195:Peroxidase / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D008315:Malondialdehyde; D002392:Catechin; C045651:epigallocatechin gallate; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase