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

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-Fe(3+ )into free Fe(2+), contributing to oxidative damage. METHODS: Liver cirrhosis was induced by CCl(4 )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

A ROLE FOR GROWTH HORMONE AND PROLACTIN IN LEUKAEMIA AND LYMPHOMA?

Growth hormone (GH) and prolactin (PRL) quality as lymphohaemopoietic growth and differentiation factors, and so does insulin-like growth factor (IGF)-I, which mediates many of GH activities. Although there is only limited evidence that endocrine, paracrine or autocrine GH or PRL play a role in human leukaemia and lymphoma, the expression of these factors or their receptors may have diagnostic or therapeutic implications. Indeed, the participation of GH, PRL or IGF-I in the development or progression of certain haematological malignancies or to the antitumour immune response has been documented. Examples discussed in this review include a rat lymphoma in which the PRL receptor acts as an oncogene; the rat Nb2 lymphoma, which is dependent on PRL for growth; and experiments showing that PRL stimulates natural killer cell activity and the development of lymphokine-activated killer cells