LIVER DISEASE

Insulin-like growth factor I improves intestinal barrier function in cirrhotic rats

V Lorenzo-Zúñiga^1,*, C M Rodríguez-Ortigosa^2,*, R Bartolí¹, M-L Martínez-Chantar², L Martínez-Peralta², A Pardo², I Ojanguren³, J Quiroga², R Planas¹, J Prieto²

¹ Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
² Department of Medicine and Liver Unit, Clínica Universitaria, Medical School and Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain
³ Department of Histology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain

Correspondence to:
Professor J Prieto
Department of Medicine and Liver Unit, Clínica Universitaria and Centre for Applied Medical Research (CIMA), University of Navarra, 31080 Pamplona, Spain; jprieto{at}unav.es

Background and aims: 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 (TNF-), 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- 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.

Abbreviations: BDL, bile duct ligation; Col1, procollagen 1(I); GH, growth hormone; IBF, intestinal barrier function; IGF-I, insulin-like growth factor type I; PHE, portal hypertensive enteropathy; SBP, spontaneous bacterial peritonitis; TER, transepithelial electrical resistance; COX-2, cyclooxygenase 2; TNF-, tumour necrosis factor ; LPS, lipopolysaccharide; CCl₄, carbon tetrachloride; DMEM, Dulbecco’s modified Eagle’s medium; FBS, fetal bovine serum; RT-PCR, reverse transcription-polymerase chain reaction

Keywords: bacterial peritonitis; hepatic fibrosis; intestinal barrier; rats

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