title: Octreotide prevents liver failure through upregulating 5'-methylthioadenosine in extended hepatectomized rats.
abstract: OBJECTIVE
  Insufficient liver regeneration and hepatocyte injury caused by excessive portal perfusion are considered to be responsible for post-hepatectomy liver failure (PLF) or small-for-size syndrome in living-donor liver transplantation. Somatostatin can decrease portal vein pressure (PVP) but simultaneously inhibits liver regeneration. This interesting paradox motivated us to investigate the outcome of PLF in response to somatostatin treatment.
  
  
  METHODS
  Rats receiving extended partial hepatectomy (90% PH) were treated with octreotide, a somatostatin analogue, or placebo. Animal survival, serum parameters and hepatic histology were evaluated. Metabolomic analysis was performed to investigate the effect of octreotide on hepatocyte metabolism.
  
  
  RESULTS
  Despite significantly inhibiting early regeneration, octreotide application noticeably improved the hepatic histology, liver function and survival after PH but did not decrease the PVP level. Metabolomic analysis exhibited that octreotide profoundly and exclusively altered the levels of five metabolites that participate in or closely associate with the methionine cycle, a biochemical reaction that uniquely produces S-adenosylmethionine (SAMe), an active methyl residual donor for methyltransferase reactions. Among these metabolites, 5'-methylthioadenosine (MTA), a derivate of SAMe, increased three-fold and was found independently improve the hepatic histology and reduce inflammatory cytokines in hepatectomized rats.
  
  
  CONCLUSIONS
  Octreotide exclusively regulates the methionine cycle reaction and augments the MTA level in hepatocytes. MTA prominently protects hepatocytes against shear stress injury and reduces the secondary inflammation, thereby protecting rats from PLF.
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.|Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.|Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Zhenggui
authors.initials: Z
authors.lastname: Du
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Changli
authors.initials: C
authors.lastname: Lu
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.|Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Bu
authors.affiliation: Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D003839:Deoxyadenosines / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D006498:Hepatectomy / Q000009:adverse effects*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D017093:Liver Failure / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000493:pharmacokinetics; D020011:Protective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D011497:Protein O-Methyltransferase / Q000037:antagonists & inhibitors; D051381:Rats; D013872:Thionucleosides / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D003839:Deoxyadenosines; D005765:Gastrointestinal Agents; D020011:Protective Agents; D013872:Thionucleosides; C008500:5'-methylthioadenosine; D011497:Protein O-Methyltransferase; D015282:Octreotide
keywords: metabolomic analysis; methionine cycle; portal perfusion; post-hepatectomy liver failure