Research article

Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis

María García-Fernández^1,2 , Inma Castilla-Cortázar^1,2,3,2 , Matías Díaz-Sanchez¹ , Iñigo Navarro⁴ , Juan Enrique Puche^2,3 , Alberto Castilla⁵ , Amelia Díaz Casares^2,3 , Encarna Clavijo⁶ and Salvador González-Barón²

¹Department of Physiology, School of Medicine, University of Navarra, Pamplona, Spain

²Department of Human Physiology. School of Medicine, University of Málaga, Spain

³Department of Physiology, School of Medicine, University of San Pablo-CEU, Madrid, Spain

⁴Department of Chemistry, School of Medicine, University of Navarra, Pamplona, Spain

⁵Department of Internal Medicine, Hospital Sierrallana, Torrelavega. Cantabria, Spain

⁶Department of Microbiology, School of Medicine, University of Málaga, Spain

author email corresponding author email

BMC Gastroenterology 2005, 5:7doi:10.1186/1471-230X-5-7

Published:	3 March 2005

Abstract

Background

The exogenous administration of Insulin-like Growth Factor-I (IGF-I) induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 μg. 100 g^-1. day^-1). Iron and copper play an important role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH) that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO) and nitric oxide (NO) are known sources of free radicals and induce reduction of ferritin-Fe³⁺ into free Fe²⁺, contributing to oxidative damage.

Methods

Liver cirrhosis was induced by CCl₄ inhalation in Wistar male rats for 30 weeks. Healthy controls were studied in parallel (n = 10). Fe and Cu were assessed by atomic absoption spectrometry and iron content was also evaluated by Perls' staining. MPO was measured by ELISA and transferrin and ferritin by immunoturbidimetry. iNOS expression was studied by immuno-histochemistry.

Results

Liver cirrhosis was histologically proven and ascites was observed in all cirrhotic rats. Compared to controls untreated cirrhotic rats showed increased hepatic levels of iron, ferritin, transferrin (p < 0.01), copper, MPO and iNOS expression (p < 0.01). However, IGF-treatment induced a significant reduction of all these parameters (p < 0.05).

Conclusion

the hepatoprotective and antifibrogenic effects of IGF-I in cirrhosis are associated with a diminution of the hepatic contents of several factors all of them involved in oxidative damage.