title: Effect of NFkappaB inhibition by CAPE on skeletal muscle ischemia-reperfusion injury.
abstract: OBJECTIVE
  Nuclear factor kappa B (NFkappaB) plays important role in the pathogenesis of skeletal muscle ischemia/reperfusion (I/R) injury. Caffeic acid phenyl ester (CAPE), a potent NFkappaB inhibitor, exhibits protective effects on I/R injury in some tissues. In this report, the effect of CAPE on skeletal muscle I/R injury in rats was studied.
  
  
  METHODS
  Wistar rats were submitted to sham operation, 120-min hindlimb ischemia, or 120-min hindlimb ischemia plus saline or CAPE treatment followed by 4-h reperfusion. Gastrocnemius muscle injury was evaluated by serum aminotransferase levels, muscle edema, tissue glutathione and malondialdehyde measurement, and scoring of histological damage. Apoptotic nuclei were determined by a terminal uridine deoxynucleotidyl transferase dUTP nick end labeling assay. Muscle neutrophil and mast cell accumulation were also assessed. Lipoperoxidation products and NFkappaB were evaluated by 4-hydroxynonenal and NFkappaB p65 immunohistochemistry, respectively.
  
  
  RESULTS
  Animals submitted to ischemia showed a marked increase in aminotransferases after reperfusion, but with lower levels in the CAPE group. Tissue glutathione levels declined gradually during ischemia to reperfusion, and were partially recovered with CAPE treatment. The histological damage score, muscle edema percentage, tissue malondialdehyde content, apoptosis index, and neutrophil and mast cell infiltration, as well as 4-hydroxynonenal and NFkappaB p65 labeling, were higher in animals submitted to I/R compared with the ischemia group. However, the CAPE treatment significantly reduced all of these alterations.
  
  
  CONCLUSIONS
  CAPE was able to protect skeletal muscle against I/R injury in rats. This effect may be associated with the inhibition of the NFkappaB signaling pathway and decrease of the tissue inflammatory response following skeletal muscle I/R.
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Alessandra R
authors.initials: AR
authors.lastname: Andrade-Silva
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Ramalho
authors.forename: Leandra N Z
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Milena
authors.initials: M
authors.lastname: Saavedra-Lopes
authors.forename: Alceu A
authors.initials: AA
authors.lastname: Jordão
authors.forename: Hélio
authors.initials: H
authors.lastname: Vanucchi
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Piccinato
authors.forename: Sérgio
authors.initials: S
authors.lastname: Zucoloto