The protective effect of CAPE on hepatic ischemia/reperfusion injury in rats.
OBJECTIVE
The transcription factor nuclear factor-kappa B (NF-kappaB) exerts a pivotal role in the pathogenesis of hepatic ischemia/reperfusion (I/R) injury. Caffeic acid phenyl ester (CAPE), a potent and specific NF-kappaB inhibitor, presents protective effects on I/R injury in some tissues. This study aimed to evaluate the effect of CAPE on hepatic I/R injury in rats.


METHODS
Wistar rats were submitted to a sham operation, 60 min ischemia, or 60 min ischemia plus saline or CAPE treatment followed by 6 h reperfusion. Liver tissue injury was evaluated by alanine aminotransferase, aspartate aminotransferase, and tissue glutathione measurement, and histological damage score. Apoptotic hepatocytes were determined by the transferase-mediated dUTP-biotin nick-end labeling assay. Hepatic neutrophil accumulation was assessed by the naphthol method. Lipid peroxidation and NF-kappaB activation were evaluated by 4-hydroxynonenal and NF-kappaB p65 immunohistochemistry, respectively.


RESULTS
Animals submitted to ischemia showed a marked increase of alanine aminotransferase and aspartate aminotransferase after reperfusion, but with lower levels in CAPE group. Tissue glutathione content declined gradually during ischemia to reperfusion and was partially recovered with CAPE treatment. The histological damage score, apoptosis index, and neutrophil infiltration, as well as 4-hydroxynonenal and NF-kappaB p65 nuclear labeling, were higher in the liver of animals submitted to I/R compared to the ischemia group. However, the CAPE treatment significantly reduced all of these alterations.


CONCLUSIONS
CAPE was able to protect the liver against normothermic I/R injury in rats. This effect may be associated with the inhibition of the NF-kappaB signaling pathway and decrease of the acute inflammatory response following I/R in the liver.
Saavedra-Lopes
Milena
M
Department of Pathology, University of São Paulo, Ribeirão Preto, SP, Brazil.
Ramalho
Fernando S
FS
Ramalho
Leandra N Z
LN
Andrade-Silva
Alessandra
A
Martinelli
Ana L C
AL
Jordão
Alceu A
AA
Castro-e-Silva
Orlando
O
Zucoloto
Sérgio
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D002109:Caffeic Acids / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000293:injuries* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D002109:Caffeic Acids; D016328:NF-kappa B; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C055494:caffeic acid phenethyl ester; D005978:Glutathione; D010626:Phenylethyl Alcohol