Williams W F, Odom J D
Department of Chemistry, University of South Carolina, Columbia 29208.
Exp Eye Res. 1987 Jun;44(6):717-30. doi: 10.1016/s0014-4835(87)80036-2.
Nuclear magnetic resonance (NMR) spectroscopy has been utilized in the study of the metabolism of intact, functioning rabbit lenses maintained in organ culture. The sorbitol pathway and aldose reductase inhibition have been studied using carbon-13 NMR spectroscopy. Incubation of lenses in high concentration [1-13C] glucose medium with and without added inhibitors allows the sorbitol pathway and glycolysis to be monitored. Various aldose reductase inhibitors have been studied and are ranked based on percentage of inhibition as follows: tolrestat greater than or equal to sorbinil greater than sulindac greater than sulindac sulfide much greater than indomethacin greater than acetylsalicylic acid greater than quercetin greater than tandearil greater than salicylic acid greater than 3,3-Tetramethyleneglutaric acid (TMG). It has been demonstrated that 13C NMR spectroscopy provides an effective method of screening potential inhibitors of aldose reductase. The aspirin substitutes ibuprofen and acetaminophen have been studied and are found to reduce sorbitol accumulation in intact rabbit lenses. The effects of myo-inositol and vitamin E on sorbitol accumulation have also been investigated. Results suggest that the various metabolic pathways within the lens are intricately connected. In a preliminary manner, the effect of diabetes on metabolism in intact lenses has been investigated using 13C NMR spectroscopy. Increased sorbitol production has been observed for diabetic lenses. 31P NMR spectroscopy has also been utilized in the study of lens metabolism and aldose reductase inhibitors. Inclusion of various inhibitors in the high concentration glucose medium results in maintenance of essentially normal phosphorus-containing metabolite levels in the lens. No clear relationship was observed between lens clarity and phosphorus metabolite levels as determined using NMR.
核磁共振（NMR）光谱已被用于研究在器官培养中维持的完整、有功能的兔晶状体的代谢。已使用碳-13 NMR光谱研究了山梨醇途径和醛糖还原酶抑制作用。在添加和不添加抑制剂的高浓度[1-13C]葡萄糖培养基中孵育晶状体，可监测山梨醇途径和糖酵解。已研究了各种醛糖还原酶抑制剂，并根据抑制百分比进行排序如下：托瑞司他大于或等于索比尼尔大于舒林酸大于舒林酸硫化物远大于吲哚美辛大于乙酰水杨酸大于槲皮素大于坦地尔大于水杨酸大于3,3-四亚甲基戊二酸（TMG）。已证明13C NMR光谱提供了一种筛选醛糖还原酶潜在抑制剂的有效方法。已研究了阿司匹林替代品布洛芬和对乙酰氨基酚，发现它们可减少完整兔晶状体中山梨醇的积累。还研究了肌醇和维生素E对山梨醇积累的影响。结果表明，晶状体内的各种代谢途径相互紧密关联。已使用13C NMR光谱初步研究了糖尿病对完整晶状体代谢的影响。已观察到糖尿病晶状体中山梨醇产量增加。31P NMR光谱也已用于晶状体代谢和醛糖还原酶抑制剂的研究。在高浓度葡萄糖培养基中加入各种抑制剂可使晶状体中含磷代谢物水平基本维持正常。使用NMR测定时，未观察到晶状体透明度与磷代谢物水平之间有明确关系。
