Lee J W, Iwatsuru M, Nishigori H
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Curr Eye Res. 1991 Jul;10(7):629-35. doi: 10.3109/02713689109013854.
Glucocorticoid-induced cataract formation appears to proceed via oxidation or peroxidation steps possibly caused by multiple activities of glucocorticoid in the living system. Attempts were made to modify GC-induced metabolic changes and prevent cataract formation using intermediates of the citric acid cycle. The compounds were applied to the embryos at 3, 10 and 20 hr after the administration of hydrocortisone succinate sodium (HC:0.25 mumol/egg) to 15-day-old eggs. At 48 hr after HC treatment the lenses were classified and analyzed. Almost all lenses were classified as stage IV-V (greater than 94%). However, the application of sodium isocitrate (IC:15 mumol/egg) which was the most potent among several intermediates tested showed a significant preventive effect against cataract formation. The administration of IC prevented the decline of GSH, the elevations of LPO and reduced the marked elevation of glucose in the lens caused by HC. The IC treatment also diminished the elevation of LPO in blood and liver. The above effects by IC on HC-induced events may be due to the action of IC in preventing the early decline of hepatic GSH caused by HC. Possibly IC was utilized as an intermediate of the citric acid cycle and a substrate for isocitrate dehydrogenase in cytosol to modify GC-induced metabolic changes.
糖皮质激素诱导的白内障形成似乎是通过氧化或过氧化步骤进行的，这可能是由糖皮质激素在生物系统中的多种活性引起的。人们尝试使用柠檬酸循环的中间产物来改变糖皮质激素诱导的代谢变化并预防白内障形成。在给15日龄鸡蛋注射氢化可的松琥珀酸钠（HC：0.25 μmol/蛋）后3、10和20小时，将这些化合物应用于胚胎。在HC处理后48小时，对晶状体进行分类和分析。几乎所有晶状体都被分类为IV-V期（大于94%）。然而，在所测试的几种中间产物中最有效的异柠檬酸钠（IC：15 μmol/蛋）的应用对白内障形成显示出显著的预防作用。IC的给药阻止了HC引起的晶状体中谷胱甘肽（GSH）的下降、脂质过氧化（LPO）的升高，并降低了葡萄糖的显著升高。IC处理还减少了血液和肝脏中LPO的升高。IC对HC诱导事件的上述影响可能是由于IC在预防HC引起的肝脏GSH早期下降中的作用。异柠檬酸钠可能被用作柠檬酸循环的中间产物和细胞质中异柠檬酸脱氢酶的底物，以改变糖皮质激素诱导的代谢变化。
