Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats
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RESEARCH
Open Access
Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats Inma Castilla-Cortázar1*, María García-Fernández2, Gloria Delgado2, Juan E Puche1, Inma Sierra1, Rima Barhoum1 and Salvador González-Barón2
Abstract Background: GH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver) in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats. Methods: Three experimental groups were included in this study: young healthy controls (yCO, 17 weeks old); untreated old rats (O, 103 weeks old); and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight-1 * day-1) for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland). Serum levels of hormones (testosterone, IGF-I and insulin) were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states). ATP synthesis in isolated mitochondria was determined by an enzymatic method. Results: Compared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS). IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations. Conclusions: We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and IGF-I levels.
Background The Insulin-like Growth Factors (IGF-I and IGF-II) are ubiquitously expressed growth factors that have profound effects on the growth and differentiation of many cell types and tissues, including cells from the CNS [1-3]. We have previously studied some conditions of “IGF-I deficiency”, such as liver cirrhosis and aging, in which replacement therapy could be considered as an effective therapeutic strategy [4-16]. In fact, the exogenous administration of low doses of IGF-I in aging rats was * Correspondence: [email protected] 1 Department of Medical Physiology, CEU-San Pablo University School of Medicine Institute of Applied Molecular Medicine (IMMA) Boadilla del Monte, 28668 Madrid, Spain Full list of author information is available at the end of the article
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