title: Insulin-like growth factor I improves intestinal barrier function in cirrhotic rats.
abstract: OBJECTIVE
  In liver cirrhosis, disruption of the intestinal barrier facilitates bacterial translocation and spontaneous bacterial peritonitis. Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesised by hepatocytes that displays hepatoprotective activities and trophic effects on the intestine. The aim of this study was to investigate the effect of IGF-I on intestinal barrier function in cirrhotic rats.
  
  
  METHODS
  In rats with carbon tetrachloride induced cirrhosis, we investigated the effect of IGF-I therapy on: (a) portal pressure; (b) intestinal histology and permeability to endotoxin and bacteria; (c) intestinal expression of cyclooxygenase 2 (COX-2) and tumour necrosis factor alpha (TNF-alpha), two factors that influence in a positive and negative manner, respectively, the integrity of the intestinal barrier; (d) intestinal permeability to 3H-mannitol in rats with bile duct ligation (BDL); and (e) transepithelial electrical resistance (TER) of polarised monolayers of rat small intestine epithelial cells.
  
  
  RESULTS
  IGF-I therapy reduced liver collagen expression and portal pressure in cirrhotic rats, induced improvement in intestinal histology, and caused a reduction in bacterial translocation and endotoxaemia. These changes were associated with diminished TNF-alpha expression and elevated COX-2 levels in the intestine. IGF-I reduced intestinal permeability in BDL rats and enhanced barrier function of the monolayers of epithelial intestinal cells where lipopolysaccharide (LPS) caused a decrease in TER that was reversed by IGF-I. This effect of IGF-I was associated with upregulation of COX-2 in LPS treated enterocytes.
  
  
  CONCLUSIONS
  IGF-I enhances intestinal barrier function and reduces endotoxaemia and bacterial translocation in cirrhotic rats. IGF-I therapy might be useful in the prevention of spontaneous bacterial peritonitis in liver cirrhosis.
authors.affiliation: Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Lorenzo-Zúñiga
authors.forename: C M
authors.initials: CM
authors.lastname: Rodríguez-Ortigosa
authors.forename: R
authors.initials: R
authors.lastname: Bartolí
authors.forename: M-L
authors.initials: ML
authors.lastname: Martínez-Chantar
authors.forename: L
authors.initials: L
authors.lastname: Martínez-Peralta
authors.forename: A
authors.initials: A
authors.lastname: Pardo
authors.forename: I
authors.initials: I
authors.lastname: Ojanguren
authors.forename: J
authors.initials: J
authors.lastname: Quiroga
authors.forename: R
authors.initials: R
authors.lastname: Planas
authors.forename: J
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects; D002251:Carbon Tetrachloride; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D017097:Electric Impedance; D004731:Endotoxins / Q000097:blood; D020895:Enterocytes / Q000201:enzymology; D007082:Ileum / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010539:Permeability; D017082:Portal Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D002251:Carbon Tetrachloride; D051546:Cyclooxygenase 2