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Enhanced actions of insulin‐like growth factor‐I and interferon‐α co‐administration in experimental cirrhosis
Author(s) -
Tutau Federico,
RodríguezOrtigosa Carlos,
Puche Juan Enrique,
Juanareerea,
Monreal Iñigo,
García Fernández María,
Clavijo Encarna,
Castilla Alberto,
Castilla Cortázar Inma
Publication year - 2009
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2008.01770.x
Subject(s) - cirrhosis , hepatic fibrosis , medicine , endocrinology , growth factor , fibrosis , hepatocyte growth factor , insulin like growth factor , liver function , transforming growth factor beta , transforming growth factor , receptor
Background: 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‐α (IFN‐α) 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‐α to Wistar rats with CCl 4 ‐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‐β (TGF‐β), α‐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‐α exerted significant effects on fibrogenesis. IGF‐I significantly increased serum albumin and HGF whereas IFN‐α‐therapy did not. The inhibition of TGF‐β expression was only observed by the effect of IFN‐α‐therapy. In addition, only the co‐administration of IGF‐I and IFN‐α 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.