Wang Hui-Li, Chen Xiang-Tao, Yin Shu-Ting, Liu Jin, Tang Ming-Liang, Wu Chuan-Yun, Ruan Di-Yun
Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Sep;378(3):303-10. doi: 10.1007/s00210-008-0307-6. Epub 2008 May 27.
Among the developmental changes identified in rats exposed to lead are impairments in long-term potentiation (LTP) in the hippocampus and changes in the levels of reactive oxygen species (ROS) in cells and some soft tissues. alpha-Lipoic acid (LA) has been reported to be highly effective in improving the thiol capacity of the cells and in reducing lead-induced oxidative stress. To explore the effects of LA on LTP in chronically lead-exposed rats and the relationship between ROS and LTP in both control and lead-exposed rats, we have compared LTP and oxidative stress parameters in groups of lead-exposed and control rats with or without LA treatment (10, 25, 50, and 100 mg/kg through intraperitoneal injection). The capacity of LA to decrease hippocampal lead levels in lead-exposed rats was examined. We found that LA had no effects in decreasing the level of lead in the hippocampus, but it did appear to have both antioxidant properties and a reparatory effect on LTP amplitude in rats developmentally exposed to lead for 2 weeks following birth. Interestingly, bell-shaped dose-response curves emerged. In the lower LA dosage groups (10, 25 mg/kg LA), there was an increasing LTP amplitude. The strongest protective effect in terms of the induction and amplitude of LTP in the lead-exposed group with at 25 mg/kg LA; when higher dosages were applied (50, 100 mg/kg LA), the LTP amplitude decreased as compared to the 25 mg/kg LA treatment group. The administration of LA to control animals resulted in a significant impairment of LTP amplitude, with the 100 mg/kg LA treatment having harmful effects on the oxidative parameters. These differential effects of LA on LTP in control and lead-exposed rats may be due to the different redox status of the control and lead-exposed rats.
在暴露于铅的大鼠中发现的发育变化包括海马体中长时程增强（LTP）受损以及细胞和一些软组织中活性氧（ROS）水平的变化。据报道，α-硫辛酸（LA）在提高细胞的硫醇能力和降低铅诱导的氧化应激方面非常有效。为了探讨LA对长期暴露于铅的大鼠LTP的影响以及对照组和铅暴露组大鼠中ROS与LTP之间的关系，我们比较了接受或未接受LA治疗（通过腹腔注射，剂量分别为10、25、50和100mg/kg）的铅暴露组和对照组大鼠的LTP和氧化应激参数。检测了LA降低铅暴露大鼠海马体铅水平的能力。我们发现，LA对降低海马体中的铅水平没有作用，但它似乎具有抗氧化特性，并且对出生后发育性暴露于铅2周的大鼠的LTP幅度具有修复作用。有趣的是，出现了钟形剂量反应曲线。在较低LA剂量组（10、25mg/kg LA）中，LTP幅度增加。在铅暴露组中，25mg/kg LA对LTP的诱导和幅度具有最强的保护作用；当应用更高剂量（50、100mg/kg LA）时，与25mg/kg LA治疗组相比，LTP幅度降低。给对照组动物注射LA导致LTP幅度显著受损，100mg/kg LA治疗对氧化参数有有害影响。LA对对照组和铅暴露组大鼠LTP的这些不同影响可能是由于对照组和铅暴露组大鼠的氧化还原状态不同。
