These results show that IGF- I exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.

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.

Background: Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. These alterations returned to normal with the administration of Insulin-Like Growth Factor-I (IGF-I). The aims of this study were to explore the evolution of these alterations and analyse the effect of IGF-I in rats with advanced cirrhosis and ascites. Thus, jejunal structure and nutrient transport (D-galactose, L-leucine, L-proline, L-glutamic acid and L-cystine) were studied in rats with ascitic cirrhosis.

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IGF-I is an anabolic hormone which has been reported to increase bone formation in several conditions of undernutrition. Advanced liver cirrhosis is associated with osteopenia and also with low serum levels of IGF-I. Previous results showed that low doses of IGF-I increase osteoblastic activity and decrease bone reabsorption in early liver cirrhosis. The aim of this study was to evaluate whether IGF-I-treatment also induces beneficial effect on osteopenia associated with advanced cirrhosis. Rats with ascitic cirrhosis were divided into two groups: group CI (n=10) which received saline and group CI+IGF (n=10) which were treated with IGF-I (2 microg/100 g bw x day, sc, during 21 days). Healthy controls which received saline were studied in parallel (CO n=10). On the 22nd day, the animals were sacrificed, and bone parameters were analyzed in femur. Posterior-anterior diameter was similar in all groups. No significant differences were observed in bone content of calcium, total proteins, collagen and hydroxyapatite in cirrhotic rats as compared with controls. However, CI rats showed significant reductions in total bone density (-13.5%, p<0.001) assessed by densitometry and radiological study. In CI+IGF rat bone density (assessed by densitometry) improved significantly as compared with CI animals. In summary, osteopenia characterized by loss of bone mass and preserved bone composition was found in rats with advanced cirrhosis induced by CCl4 and phenobarbital in drinking water. This bone disorder is partially restored by treatment with low doses of IGF-I during only three weeks. Thus, IGF-I could be considered as a possible therapy for osteopenia associated with advanced liver cirrhosis.