title: The effect of octreotide on hepatic ischemia-reperfusion injury in a rabbit model.
abstract: BACKGROUND
  Hepatic ischemic-reperfusion injury (HIRI) is a major cause of morbidity and mortality following liver surgery. Octreotide (Oct) has been reported to improve hepatocellular energy metabolism in a rat HIRI model. This study was designed to evaluate whether Oct could protect the liver of rabbits against ischemic-reperfusion (I/R) injury.
  
  
  METHODS
  Twenty-four adult New Zealand rabbits were randomly divided into a sham operated group (Control), an ischemia/reperfusion group (I/R), and an ischemia/reperfusion + Oct pretreatment group (I/R + Oct). The hemodynamic (mean arterial pressure [MAP] and heart rate [HR]) changes, liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]) release, inflammatory cytokines (tumor necrosis factor [TNF]α and interleukin [IL]-1β) levels, and endotoxin (ETX) levels were measured during I/R.
  
  
  RESULTS
  Compared with the Control group, the MAP decreased and HR increased in I/R and I/R + Oct groups at ischemia 15 minutes (P < .05) but were less in the I/R + Oct group relative to the I/R group (P < .05). ALT, AST, LDH, IL-1β, and ETX levels were increased in the I/R and I/R + Oct groups at ischemia 30 minutes (P < .05), however, the increase was lower in the I/R + Oct group relative to the I/R group (P < .05). Bcl-2 expression in the I/R + Oct group was higher compared with other groups (P < .05) and Bax expression in the I/R group was reduced compared with other groups (P < .05). Hepatocellular damage in the I/R + Oct group appeared to be less than in the I/R group by microscopy.
  
  
  CONCLUSIONS
  Oct pretreatment attenuated hemodynamic changes and decreased liver enzyme changes induced by HIRI in a rabbit model. The protection mechanisms of Oct may be related to reduced ETX levels, down-regulation of the inflammatory cytokines TNFα and IL-1β, and inhibition of hepatocellular apoptosis, as well as the modulation of the mitochondrion-mediated Bcl-2/Bax apoptosis pathway. Based on our study it appears that Oct may be useful in decreasing liver injury after liver surgery and/or transplantation and may serve as a promising agent against HIRI.
authors: Department of Anesthesiology of Affiliated Tumor Hospital of Xiang-Ya Medical College of Central South University, Changsha, China. 315977705@qq.com
authors: J
authors: J
authors: Yang
authors: H
authors: H
authors: Sun
authors: P
authors: P
authors: Takacs
authors: Y
authors: Y
authors: Zhang
authors: J
authors: J
authors: Liu
authors: Y
authors: Y
authors: Chang
authors: K A
authors: KA
authors: Candiotti
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D062186:Arterial Pressure / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood; D004734:Energy Metabolism / Q000187:drug effects; D004798:Enzymes / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D018836:Inflammation Mediators / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008107:Liver Diseases / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004731:Endotoxins; D004798:Enzymes; D018836:Inflammation Mediators; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D015282:Octreotide