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

Vicente Lorenzo-Zuñiga ¹, Carlos M Rodriguez-Ortigosa ², Ramon Bartoli ¹, Maria Luz Martinez-Chantar ³, Laura Martinez-Peralta ³, Ana Pardo ³, Isabel Ojanguren ¹, Jorge Quiroga ⁴, Ramon Planas ¹ and Jesus Prieto ^5*

¹ Hospital Universitari Germans Trias i Pujol. Badalona, Spain
² University of Navarra. Center for Applied Medical Research (CIMA), Spain
³ Center for Applied Medical Research (CIMA). University of Navarra, Spain
⁴ Department of Medicine and Liver Unit, Clínica Universitaria. Pamplona, Spain
⁵ University of Navarra. Department of Medicine and Liver Unit, Clínica Universitaria. Pamplona, Spain

^* To whom correspondence should be addressed. E-mail: jprieto{at}unav.es.

Accepted 17 January 2006

Abstract

Background and aims: In liver cirrhosis disruption of intestinal barrier facilitates bacterial translocation and spontaneous bacterial peritonitis. Insulin-like growth factor-I (IGF-I) is an anabolic hormone synthesized 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 CCl₄-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 COX2 and TNF, two factors that influence in a positive and negative manner, respectively, the integrity of the intestinal barrier, d) the intestinal permeability to ³H-mannitol in rats with bile duct ligation (BDL) and e) the transepithelial electrical resistance (TER) of polarized monolayers of rat small intestine epithelial cells.

Results: IGF-I therapy reduced liver collagen expression and portal pressure in cirrhotic rats, induced an improvement of intestinal histology and caused a reduction of bacterial translocation and endotoxemia. These changes were associated with diminished TNF expression and elevated COX-2 levels in the intestine. IGF-I reduced the intestinal permeability in BDL rats and enhanced the barrier function of monolayers of epithelial intestinal cells where LPS caused a decrease of 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 endotoxemia and bacterial translocation in cirrhotic rats. IGF-I therapy might be useful in the prevention of spontaneous bacterial peritonitis in liver cirrhosis.

Keywords: COX-2, TNFalpha, bacterial peritonitis, hepatic fibrosis, intestinal barrier

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