Effect of α-ketoglutarate against selenite cataract formation
Effect of α-ketoglutarate against selenite cataract formation
复制标题
DOI：
10.1016/j.exer.2004.06.012
复制
发表时间：
2004-12-01
影响因子：
3.4
通讯作者：
Hegde, KR
中科院分区：
文献类型：
--
作者：
Varma, SD;Hegde, KR
我们先前已经证明丙酮酸盐在体外保护透镜免受活性氧（ROS）诱导的损伤。它对白内障的发展也有显着的效果。其有效性归因于分子中存在α-酮基羧酸基团，作为ROS的清除剂。因此，认为需要确定其他α-酮酸是否具有类似的作用。因此，使用α-酮戊二酸（α-KG）进行了这些研究，α-酮戊二酸是一种具有更高稳定性且对糖酵解无任何已知显著影响的化合物。通过监测给予亚硒酸钠的幼鼠白内障的发展来评估其有效性。大部分动物（约80%）在给药后7-8天出现核混浊。在用α-酮戊二酸治疗的动物中，白内障的发生率仅为23%。因此，该试剂具有非常显著的抗白内障作用，如通过直接裂隙灯检查随后摄影以及通过透照检查分离的晶状体所示。眼科发现的意义也是显而易见的，更好的生理维护的组织，反映了更高水平的ATP和GSH。鉴于这些体内有益作用，正在进行研究以确定其作用的生化和代谢位点。其有效性是否仅与其作为ROS清除剂的作用有关，或者也可能由一些独立于ROS的代谢作用贡献，仍有待确定。(C)2004爱思唯尔有限公司保留所有权利。
We have previously shown that pyruvate protects against reactive oxygen species (ROS) induced damage to lens in vitro. It has also a significant effect against cataract development. Its effectiveness has been ascribed to the presence of alpha-keto-carboxylate group in the molecule, acting as a scavenger of ROS. Hence, it was felt desirable to determine if other alpha-keto-acids could have similar effects. These studies have hence been conducted with alpha-ketoglutarate (alpha-KG), a compound with greater stability and without any known significant effect on the glycolysis. Its effectiveness has been assessed by monitoring cataract development in rat pups given sodium selenite. A large percentage of such animals (about 80%) developed nuclear opacity 7-8 days after its administration. In animals treated with alpha-ketoglutarate, the incidence of cataracts was only 23%. The agent therefore has a very substantial anti cataractogenic effect, as apparent by direct slit lamp examination followed by photography, as well as by examination of the isolated lenses through transillumination. The significance of the ophthalmologic findings was apparent also by better physiological maintenance of the tissue, reflected by higher levels of ATP and GSH. In view of these in vivo beneficial effects, studies are in progress to identify the biochemical and metabolic sites of its action. Whether the effectiveness is related only to its action as a ROS scavenger or it Could be contributed also by some metabolic effects independent of ROS remains to be determined. (C) 2004 Elsevier Ltd. All rights reserved.