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

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-Fe 3+ into free Fe 2+ , contributing to oxidative damage.

IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture

“…The lack of expression of the IGF-1 receptor in animals that have not received any injury seems to mean that it is a “defense mechanism,” as previous results suggested [4, 21, 35, 40, 41, 45]. Such defense mechanism allows the liver to take advantage of the beneficial actions of this hormone following injury.…”

“…The preference for IGF-1 treatment at low doses was chosen following the experience acquired from previous studies belonging to the same model [4–6, 8, 9, 11, 13, 14, 18, 21, 24, 35, 39, 40, 45]. Briefly, such dosage is enough to restore normal circulating IGF-1 values without inducing hypoglycemia and any adverse effects.…”

Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease

“…These cytokines are reported to have a pivotal role in development of NAFLD [24,25], therefore, this may account for the decreased IGF-1 level and reduced IGF-1/ IGFBP-3 ratio in advanced NASH and the negative correlation of these variables with the hyarulonic acid level. Based on the success of IGF-1 replacement therapy in animal models [26,27], this therapy has recently been used for patients with liver cirrhosis [28]. IGF-1 supplementation protects the liver from damage, increases the albumin concentration and resting energy expenditure.…”

Protection Against Oxidative Stress and “IGF-I Deficiency Conditions”

“…In these experimental groups we measured the oxidative stress by determination of: Total serum antioxidant status [40], liver contents of pro-oxidative metals [138] (iron and copper), parameters of oxidative damage such as lipid peroxidation (MDA), protein carboxyl content (PCC) and activities of antioxidant enzymes in homogenates of brain and liver.…”

“…Experimental model of cirrhosis: Male Wistar rats in which liver cirrhosis was inducted using CCl4. IGF-I therapy or saline was administrated the last 4 weeks [2,6,41,[137][138][139]. b.…”