Enhanced actions of insulin-like growth factor-I and interferon-I- co-administration in experimental cirrhosis

• Published in: Liver international Vol. 29; pp. 37 - 46
• Main Authors: Tutau, Federico, Rodriguez-Ortigosa, Carlos, Puche, Juan Enrique, Juanarena, Nerea, Monreal, Inigo, Garcia Fernandez, Maria, Clavijo, Encarna, Castilla, Alberto, Castilla - Cortazar, Inma
• Format: Journal Article
• Language: English
• Published: 01.01.2009
• ISSN: 1478-3223; 1399-1698
• DOI: 10.1111/j.1478-3231.2008.01770.x

AbstractBackground: Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation. The liver is the major source of circulating insulin-like growth factor-I (IGF-I) whose plasma levels are diminished in cirrhosis. IGF-I supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects. On other hand, interferon-a (IFN-a) therapy seems to suppress the progression of hepatic fibrosis.Aims: The aim of this study was to investigate the effect of the co-administration of IGF-I+IFN-a to Wistar rats with CCl4-induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology.Methods: The mechanisms underlying the effects of these agents were studied by reverse transcription-polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor-b (TGF-b), a-smooth muscle actin, collagen, tissular inhibitor of metalloproteinases-1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection.Results: Both IGF-I and IFN-a exerted significant effects on fibrogenesis. IGF-I significantly increased serum albumin and HGF whereas IFN-a-therapy did not. The inhibition of TGF-b expression was only observed by the effect of IFN-a-therapy. In addition, only the co-administration of IGF-I and IFN-a was able to increase the PXR. The combined therapy with both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture.Conclusion: The co-administration IGF-I+IFN enhanced all the beneficial effects observed with each factor separately, showing an additive action on histopathology and PXR expression, which is involved in the inhibition of fibrogenesis.