Simard-Duquesne N, Greselin E, Gonzalez R, Dvornik D
Proc Soc Exp Biol Med. 1985 Apr;178(4):599-605. doi: 10.3181/00379727-178-42048.
With a fixed time period of galactose feeding, the rate of appearance of lenticular opacities depended on the severity of galactosemia, while with a fixed amount of galactose fed, the rate was time dependent. The capacity of tolrestat, a structurally novel inhibitor of aldose reductase (AR), to control cataract development was assessed in rats fed 30-50% galactose with the diet for 7 to 277 days. In rats fed 30% galactose for 31 days, the controlling effect of tolrestat was dose dependent, and no cataracts were detected at a dose of 35 mg/kg/day. In rats given tolrestat with the diet for 14 days, then rendered severely galactosemic with a diet containing 50% galactose, and subjected to continued treatment with tolrestat at a dose of 43 mg/kg/day, no changes were detected by slit-lamp microscopy after 207 days. The preventive effect was also dose dependent. In view of the established similarity in the pathogenesis of galactosemic and diabetic cataracts, the results obtained with tolrestat support its potential for controlling cataract development in diabetics.
在固定的半乳糖喂养时间段内，晶状体混浊出现的速率取决于半乳糖血症的严重程度，而在喂食固定量半乳糖的情况下，该速率则随时间变化。在喂食含30%-50%半乳糖饮食7至277天的大鼠中，评估了一种结构新颖的醛糖还原酶（AR）抑制剂托瑞司他控制白内障发展的能力。在喂食30%半乳糖31天的大鼠中，托瑞司他的控制作用呈剂量依赖性，在剂量为35毫克/千克/天时未检测到白内障。在喂食含托瑞司他饮食14天的大鼠中，随后给予含50%半乳糖的饮食使其严重半乳糖血症，并以43毫克/千克/天的剂量继续用托瑞司他治疗，207天后裂隙灯显微镜检查未发现变化。预防效果也呈剂量依赖性。鉴于已确定半乳糖血症性白内障和糖尿病性白内障发病机制相似，托瑞司他的研究结果支持其在控制糖尿病患者白内障发展方面的潜力。
