Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, México City, Mexico.
Basic Clin Pharmacol Toxicol. 2011 Nov;109(5):350-6. doi: 10.1111/j.1742-7843.2011.00738.x. Epub 2011 Jul 12.
In this work, the effect of a single dose of diazepam was tested on different markers of oxidative damage in the striatum of rats in an acute model of immobilization (restraint) stress. In addition, the locomotor activity was measured at the end of the restraint period. Immobilization was induced to animals for 24 hr, and then, lipid peroxidation, superoxide dismutase activity and content, and mitochondrial function were all estimated in striatal tissue samples. Corticosterone levels were measured in serum. Diazepam was given to rats as a pre-treatment (1 mg/kg, i.p.) 20 min. before the initiation of stress. Our results indicate that acute stress produced enhanced striatal levels of lipid peroxidation (73% above the control), decreased superoxide dismutase activity (54% below the control), reduced levels of mitochondrial function (35% below the control) and increased corticosterone serum levels (86% above the control). Pre-treatment of stressed rats with diazepam decreased the striatal lipid peroxidation levels (68% below the stress group) and improved mitochondrial function (18% above the stress group), but only mild preservation of superoxide dismutase activity was detected (17% above the stress group). In regard to the motor assessment, only the stereotyped activity was increased in the stress group with respect to control (46% above the control), and this effect was prevented by diazepam administration (30% below the stress group). The preventive actions of diazepam in this acute model of stress suggest that drugs exhibiting anxiolytic and antioxidant properties might be useful for the design of therapies against early acute phases of physic stress.
在这项工作中，研究人员测试了单剂量地西泮对束缚应激急性模型大鼠纹状体中不同氧化损伤标志物的影响。此外，还在束缚期结束时测量了运动活性。将动物束缚 24 小时，然后评估纹状体组织样本中的脂质过氧化、超氧化物歧化酶活性和含量以及线粒体功能。测量血清中的皮质酮水平。地西泮作为预处理（1mg/kg，ip），在应激开始前 20 分钟给予大鼠。结果表明，急性应激导致纹状体脂质过氧化水平升高（比对照组高 73%），超氧化物歧化酶活性降低（比对照组低 54%），线粒体功能降低（比对照组低 35%），血清皮质酮水平升高（比对照组高 86%）。应激大鼠预先用地西泮处理可降低纹状体脂质过氧化水平（比应激组低 68%），改善线粒体功能（比应激组高 18%），但超氧化物歧化酶活性仅轻度保存（比应激组高 17%）。关于运动评估，只有应激组的刻板活动相对于对照组增加（比对照组高 46%），而地西泮给药可预防这种作用（比应激组低 30%）。地西泮在这种急性应激模型中的预防作用表明，具有抗焦虑和抗氧化特性的药物可能有助于设计针对物理应激早期急性阶段的治疗方法。
