Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats.
Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats.
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DOI：
10.1186/1479-5876-9-103
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发表时间：
2011-07-06
影响因子：
7.4
通讯作者：
González-Barón S
中科院分区：
文献类型：
--
作者：
Castilla-Cortázar I;García-Fernández M;Delgado G;Puche JE;Sierra I;Barhoum R;González-Barón S
血清GH和IGFs水平随年龄增长而下降。维生素C相关的变化似乎与这些合成代谢激素的减少有关。我们以前已经证明，IGF-I替代疗法可以改善胰岛素抵抗，脂质代谢，并减少氧化损伤（在大脑和肝脏）在老龄大鼠。使用相同的实验模型，这项工作的目的是研究是否外源性管理的IGF-II，在低剂量下，类似于IGF-I在老龄大鼠的行为。本研究包括三个实验组：年轻健康对照组（yCO，17周龄）;未治疗的老年大鼠（0，103周龄）;和用IGF-II治疗的老年大鼠（0 +IGF-II，2 μg * 100 g体重-1 * 天-1）30天。使用自动分析仪（Cobas Mira; Roche诊断系统，巴塞尔，瑞士），通过常规实验室方法测定血清中的分析参数。采用放射免疫分析法测定血清睾酮、胰岛素样生长因子-I（IGF-I）和胰岛素水平。血清总抗氧化状态采用比色法进行评价。使用罗丹明123染料（添加不同底物以确定不同状态）评估线粒体膜电位。用酶法测定线粒体ATP合成。与年轻对照组相比，未处理的老年大鼠显示IGF-I和睾酮水平降低，血清总抗氧化状态（TAS）降低。IGF-II治疗改善血清抗氧化能力，而不改变睾酮和IGF-I循环浓度。此外，IGF-II治疗减少了大脑和肝脏的氧化损伤，改善了抗氧化酶活性和线粒体功能。IGF-II还能够降低胆固醇和甘油三酯水平，增加游离脂肪酸浓度。我们证明，低剂量的IGF-II诱导肝脏保护，神经保护和代谢作用，改善线粒体功能，而不影响睾酮和IGF-I水平。
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. 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. 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. We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and IGF-I levels.
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影响因子：
13
作者：
Clemmons, David R.
通讯作者：
Clemmons, David R.
DOI：
10.1016/s1357-2725(01)00123-6
发表时间：
2002-03-01
影响因子：
4
作者：
Mirpuri, E;García-Trevijano, ER;Avila, MA
通讯作者：
Avila, MA
影响因子：
29.4
作者：
CastillaCortazar, I;Garcia, M;Prieto, J
通讯作者：
Prieto, J
影响因子：
64.8
作者：
HOGEBOOM, GH;SCHNEIDER, WC
通讯作者：
SCHNEIDER, WC
影响因子：
4.1
作者：
Garcia-Segura, Luis M.;Sanz, Amaya;Mendez, Pablo
通讯作者：
Mendez, Pablo