Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions
Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions
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DOI：
10.1016/j.expneurol.2007.12.029
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发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Massieu, Lourdes
中科院分区：
文献类型：
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作者：
Haces, Maria L.;Hernandez-Fonseca, Karla;Massieu, Lourdes
酮体在哺乳动物哺乳期的能量代谢中起着重要作用。正常情况下，成年期酮体的血液浓度非常低，但在饥饿、外源性输注或生酮饮食期间可能会升高。每当酮体的水平增加时，它们在大脑中的氧化就会增加。由于这个原因，它们已被用作对抗难治性癫痫的保护性分子以及用于缺血和兴奋性毒性的实验模型。这些化合物的保护作用的机制尚未完全了解。在这里，我们研究了酮体可能的抗氧化能力，以及它是否有助于防止低血糖期间诱导的氧化损伤。我们报告的第一次的酮体，乙酰乙酸（AcAc）和β-羟基丁酸（D-和L-BHB，分别）的生理和非生理异构体的清除能力，为不同的活性氧（ROS）。D-和L-BHB能有效地清除羟自由基（（OH）-O-中心点）。此外，三种酮体能够减少糖酵解抑制剂碘乙酸（IOA）诱导的细胞死亡和ROS产生，而只有D-BHB和AcAc阻止神经元ATP下降。最后，在胰岛素诱导的低血糖症的体内模型中，施用D-或L-BHB，但不施用AcAc，能够防止低血糖症诱导的大鼠海马中脂质过氧化的增加。我们的数据表明，在与自由基产生和能量损伤相关的体外和体内模型中，抗氧化能力有助于保护酮体免受氧化损伤。(C)2008年爱思唯尔公司All rights reserved.
Ketone bodies play a key role in mammalian energy metabolism during the suckling period. Normally ketone bodies' blood concentration during adulthood is very low, although it can rise during starvation, an exogenous infusion or a ketogenic diet. Whenever ketone bodies' levels increase, their oxidation in the brain rises. For this reason they have been used as protective molecules against refractory epilepsy and in experimental models of ischemia and excitotoxicity. The mechanisms underlying the protective effect of these compounds are not completely understood. Here, we studied a possible antioxidant capacity of ketone bodies and whether it contributes to the protection against oxidative damage induced during hypoglycemia. We report for the first time the scavenging capacity of the ketone bodies, acetoacetate (AcAc) and both the physiological and non-physiological isomers of beta-hydroxybutyrate (D- and L-BHB, respectively), for diverse reactive oxygen species (ROS). Hydroxyl radicals ((OH)-O-center dot) were effectively scavenged by D- and L-BHB. In addition, the three ketone bodies were able to reduce cell death and ROS production induced by the glycolysis inhibitor, iodoacetate (IOA), while Only D-BHB and AcAc prevented neuronal ATP decline. Finally, in an in vivo model of insulin-induced hypoglycemia, the administration Of D- or L-BHB, but not of AcAc, was able to prevent the hypoglycemia-induced increase in lipid peroxidation in the rat hippocampus. Our data suggest that the antioxidant capacity contributes to protection of ketone bodies against oxidative damage in in vitro and in vivo models associated with free radical production and energy impairment. (C) 2008 Elsevier Inc. All rights reserved.