title: Relationship between ischemia/reperfusion injury and the stimulus of fibrogenesis in an experimental model: comparison among different preservation solutions.
abstract: OBJECTIVE
  Orthotopic liver transplantation (OLT) has been the standard treatment for end-stage acute and chronic liver disease. Ischemia-reperfusion (I/R) injury is one of the major causes of poor graft function early after OLT, and adversely influencing graft and patient survivals. It is unknown whether I/R injury influences liver fibrogenesis.
  
  
  METHODS
  Livers from 25 adult male Wistar rats were randomly assigned into 5 experimental groups according to the preservation solution: saline solution (SS); University of Wisconsin (UW) solution; Fructose 1, 6-biphosphate (FBP); S-Nitroso-N-Acetylcysteine (SNAC): or UW+SNAC (SNAC+UW). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) were determined in preservation solution samples at 2, 4, and 6 hours. After 6 hours of cold ischemia, ex situ reperfusion was applied to the liver for 15 minutes. Serum AST, ALT, LDH, and renin levels were determined. Fresh liver slices were processed for histological studies, determination of thiobarbituric acid reactive substances, catalase, and glutathione, and expression of TGF-β1 and angiotensin II AT1 receptor.
  
  
  RESULTS
  AST was significantly lower during cold storage with UW than with the older media (P=.001); ALT was lower in the FBP group (P=.023) and LDH was lower in the FBP and SNAC groups (P=.007). After reperfusion, serum AST, ALT, LDH, and TBARS showed no significant differences among the groups. Catalase was significantly lower in the SS and FBP groups (P=.008 and P=.006, respectively). Compared with UW, glutathione concentrations were significantly higher in SS, FBP, and SNAC 200 (P=.004). Renin levels were significantly lower in the FBP group (P=.022). No histological signs of preservation injury were observed in the hepatic sample. No expressions were detected of TGF-β1 or AT1 receptor.
  
  
  CONCLUSIONS
  In this experimental model of early reperfusion injury, preservation changes related to higher levels of renin, which suggest its role in fibrogenesis. FBP was associated with lower renin levels than other solutions including UW.
authors.affiliation: School of Medicine, Universidade Federal do Rio Grande do Sul/Hospital de Clínicas de Porto Alegre, Brazil. vrcamachoterra.com.br
authors.forename: V R
authors.initials: VR
authors.lastname: Camacho
authors.forename: R S
authors.initials: RS
authors.lastname: de Fraga
authors.forename: R S
authors.initials: RS
authors.lastname: Fraga
authors.forename: C T
authors.initials: CT
authors.lastname: Cerski
authors.forename: J R
authors.initials: JR
authors.lastname: de Oliveira
authors.forename: J R
authors.initials: JR
authors.lastname: Oliveira
authors.forename: M R
authors.initials: MR
authors.lastname: Álvares-da-Silva
authors.forename: M R
authors.initials: MR
authors.lastname: Alvares-Dasilva
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005635:Fructosediphosphates / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D019188:Organ Preservation Solutions / Q000737:chemistry / Q000494:pharmacology*; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012083:Renin / Q000097:blood; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005635:Fructosediphosphates; D007328:Insulin; D019188:Organ Preservation Solutions; D044140:Receptor, Angiotensin, Type 1; C508962:Tgfb1 protein, rat; D017392:Thiobarbituric Acid Reactive Substances; D053773:Transforming Growth Factor beta1; C055206:University of Wisconsin-lactobionate solution; C024940:S-nitroso-N-acetylcysteine; D000493:Allopurinol; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D012083:Renin; D005978:Glutathione; D000241:Adenosine; C029063:fructose-1,6-diphosphate; D011887:Raffinose; D000111:Acetylcysteine