Unakar N J, Tsui J Y, Johnson M J
Department of Biological Sciences, Oakland University, Rochester, MI 48309-4401.
Curr Eye Res. 1989 Oct;8(10):997-1010. doi: 10.3109/02713688908997392.
Our recent investigations have shown that the Eisai compound, E-0722, (2R-4S-6-fluoro-1-2-methylspirochroman 4,4'-imidazolidine 2,5'-dione) is a more potent aldose reductase inhibitor than Sorbinil (D-6-fluorospirochroman 4,4'-imidazolidine 2,5'-dione). In the previous studies these aldose reductase inhibitors were added to the 50% galactose diet fed to rats to determine their effect on galactose-induced alterations in the lens and the development of cataract. In this report we present our results on the effect of prefeeding the aldose reductase inhibitor, E-0722, on the alterations in rat lens following subsequent feeding of galactose. For this study, young Sprague Dawley rats were prefed either rat chow or rat chow plus 50% galactose containing 1mg/day/Kg body weight of E-0722 for 1 or 2 weeks. After this dietary regimen, the animals were transferred to diets containing 50% galactose for different periods. For controls, rats were fed either rat chow or 50% galactose without the prefeeding of E-0722. Our results obtained through gross observation of the lenses, light microscopic studies of lens sections and assay of Na+-K+-ATPase (NPPase) activity show that the prefeeding of E-0722 prior to galactose feeding delays galactose-induced alterations and the development of mature cataract.
我们最近的研究表明，卫材化合物E-0722（2R-4S-6-氟-1-2-甲基螺色满4,4'-咪唑烷2,5'-二酮）是一种比索比尼尔（D-6-氟螺色满4,4'-咪唑烷2,5'-二酮）更有效的醛糖还原酶抑制剂。在先前的研究中，将这些醛糖还原酶抑制剂添加到喂食大鼠的50%半乳糖饮食中，以确定它们对半乳糖诱导的晶状体改变和白内障形成的影响。在本报告中，我们展示了预先喂食醛糖还原酶抑制剂E-0722对随后喂食半乳糖后大鼠晶状体改变的影响的结果。在本研究中，将年轻的斯普拉格-道利大鼠预先喂食大鼠饲料或大鼠饲料加50%半乳糖（含1mg/天/千克体重的E-0722）1或2周。经过这种饮食方案后，将动物转移到含50%半乳糖的不同时间段的饮食中。作为对照，给大鼠喂食大鼠饲料或50%半乳糖，不预先喂食E-0722。我们通过对晶状体的大体观察、晶状体切片的光学显微镜研究以及Na+-K+-ATP酶（NPP酶）活性测定获得的结果表明，在喂食半乳糖之前预先喂食E-0722可延迟半乳糖诱导的改变和成熟白内障的形成。
