Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats
Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats
复制标题
DOI：
10.1006/exer.1998.0502
复制
发表时间：
1998-08-01
影响因子：
3.4
通讯作者：
Sato, S
中科院分区：
文献类型：
--
作者：
Kador, PF;Inoue, J;Sato, S
最近几项关于山梨糖醇脱氢酶原a se抑制剂4-[4-（N，N-二甲基氨磺酰基）哌嗪基]-2-甲基嘧啶（SDH-1）及其活性代谢产物4-[4-（N，N-二甲基氨磺酰基）哌嗪基]-2-羟甲基嘧啶，SDH-2，这表明山梨醇脱氢酶抑制可能有益于延迟糖尿病并发症的发作，因为它们能够改善与多元醇相关的氧化还原变化新陈代谢.为了比较山梨醇脱氢酶与醛糖还原酶抑制对糖性白内障形成的相对重要性，在用/不用山梨醇脱氢酶抑制剂SDH-1或SDH-2或醛糖还原酶抑制剂AL 1576或Ponalrestat处理的50%半乳糖喂养的糖尿病大鼠中监测白内障形成。对于这些研究，用链脲佐菌素在50 g的幼鼠中诱导糖尿病，同时通过喂食含有50%半乳糖的饮食来产生半乳糖血症。在饮食中给予抑制剂，饮食含有0.06%（w/w）山梨醇脱氢酶抑制剂或Ponalrestat和0.0125%（w/w）AL 1576。通过手持式裂隙灯监测白内障形成，并通过气相色谱法测量多元醇水平。糖性白内障形成加速糖尿病大鼠与山梨醇脱氢酶抑制剂治疗，而白内障形成没有差异，在半乳糖喂养的大鼠与/不SDH抑制剂治疗。在糖尿病和半乳糖血症大鼠中，Ponalrestat或AL 1576均可抑制白内障形成。这些结果支持了糖性白内障形成是由醛糖还原酶催化的细胞内多元醇积累引发的概念，并且这些糖性白内障可以通过抑制醛糖还原酶来预防。(C)北京：科学出版社.
Several recent studies with the sorbitol dehydro gen a se inhibitors 4-[4-(N,N-dimethylsulfamoyl)piperazino]-2-methylpyrimidine, SDH-1, and its active metabolite 4-[4-(N, N-dimethylsulfamoyl)piperazino]-2-hydroxymethylpyrimidine, SDH-2, suggest that inhibition of sorbitol dehydrogenase may be beneficial in delaying the onset of diabetic complications due to their ability to ameliorate redox changes associated with polyol metabolism. To compare the relative importance of sorbitol dehydrogenase versus aldose reductase inhibition on sugar cataract formation, cataract formation was monitored in 50% galactose-fed and diabetic rats treated with/without the sorbitol dehydrogenase inhibitors SDH-1 or SDH-2 or the aldose reductase inhibitors AL 1576 or Ponalrestat, For these studies, diabetes was induced in young 50 g rats with streptozotocin while galactosemia was produced by feeding a diet containing 50% galactose. Inhibitors were administered in the diet with the diet containing 0.06% (w/w) of the sorbitol dehydrogenase inhibitors or Ponalrestat, and 0.0125% (w/w) of AL 1576. Cataract formation was monitored by hand-held slit lamp and polyol levels were measured by gas chromatography. Sugar cataract formation was accelerated in diabetic rats treated with sorbitol dehydrogenase inhibitors while no difference in cataract formation was observed in galactose-fed rats treated with/without SDH inhibitors. Cataract formation was inhibited in both diabetic and galactosemic rats by either Ponalrestat or AL 1576. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalysed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase. (C) 1998 Academic Press.