Dehydroepiandrosterone administration counteracts oxidative imbalance and advanced glycation end product formation in type 2 diabetic patients
Dehydroepiandrosterone administration counteracts oxidative imbalance and advanced glycation end product formation in type 2 diabetic patients
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DOI：
10.2337/dc07-1110
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发表时间：
2007-11-01
期刊：
影响因子：
16.2
通讯作者：
Boccuzzi, Giuseppe
中科院分区：
文献类型：
--
作者：
Brignardello, Enrico;Runzo, Cristina;Boccuzzi, Giuseppe
目的 - 在多种体内和体外模型中，脱氢表雄酮 (DHEA) 已被证明可以预防氧化应激。本研究旨在评估 DHEA 给药对 2 型糖尿病患者氧化应激、戊糖素浓度和肿瘤坏死因子 (TNF)-α/TNF-α 受体系统活性的影响。 研究设计和方法 - 20 名患者纳入研究，并随机分配到 DHEA (n = 10) 组或安慰剂 (n = 10) 组。二十名性别和年龄匹配、血糖水平正常的健康受试者作为对照受试者。 DHEA 每天单次服用 50 毫克，持续 12 周。 结果 - 糖尿病患者的氧化应激参数显着高于对照组。糖尿病患者的戊糖素水平以及可溶性 TNF 受体 (sTNF-R)I 和 sTNF-RII 也较高。服用 DHEA 后，活性氧和羟基壬烯醛的血浆水平分别下降了 53% 和 47%，而非酶抗氧化剂谷胱甘肽和维生素 E 则增加（分别增加了 38% 和 +76%）。在外周血单核细胞（PBMC）中检测到氧化参数的相同变化。 DHEA 治疗还导致糖尿病患者的戊糖素血浆浓度显着降低（-50%）。此外，在 DHEA 治疗后，血浆和 PBMC 中的 TNF-β/TNF-α 受体系统的激活程度较低。 结论 - 数据表明 DHEA 治疗可改善高血糖引起的氧化失衡，下调 TNF-α/TNF-α 受体系统，并防止晚期糖基化终产物的形成，这表明 对 2 型糖尿病患者慢性并发症的发生和/或进展具有有益作用。
OBJECTIVE - Dehydroepiandrosterone (DHEA) has been shown to prevent oxidative stress in several in vivo and in vitro models. This study aimed to evaluate the effects of DHEA administration on oxidative stress, pentosidine concentration, and tumor necrosis factor (TNF)-alpha/TNF-alpha receptor system activity in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS - Twenty patients were enrolled in the study and randomly assigned to the DHEA (n = 10) or placebo (n = 10) group. Twenty healthy sex- and age-matched subjects with normal glucose levels served as control subjects. DHEA was given as a single daily dose of 50 mg for 12 weeks.RESULTS - Oxidative stress parameters were significantly higher in diabetic patients versus control subjects. Pentosidine levels, as well as soluble TNF receptor (sTNF-R)I and sTNF-RII, were also higher in diabetic patients. After DHEA, plasma levels of reactive oxygen species and hydroxynonenal dropped by 53 and 47%, respectively, whereas the nonenzymatic antioxidants glutathione and vitamin E increased (+38 and +76%, respectively). The same changes in oxidative parameters were detected in peripheral blood mononuclear cells (PBMCs). DHEA treatment also induced a marked decrease of pentosidine plasma concentration in diabetic patients (-50%). Moreover, the TNF-beta/TNF-alpha receptor system was shown to be less activated after DHEA treatment, in both plasma and PBMCs.CONCLUSIONS - Data indicate that DHEA treatment ameliorates the oxidative imbalance induced by hyperglycemia, downregulates the TNF-alpha/TNF-alpha receptor system, and prevents advanced glycation end product formation, suggesting a beneficial effect on the onset and/or progression of chronic complications in type 2 diabetic patients.