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醛糖还原酶抑制剂与大鼠半乳糖性白内障的预防

Aldose reductase inhibitors and prevention of galactose cataracts in rats.

作者信息

Unakar N, Tsui J, Johnson M

机构信息

Department of Biological Sciences, Oakland University, Rochester, Michigan 48309-4401.

出版信息

Invest Ophthalmol Vis Sci. 1989 Jul;30(7):1623-32.

PMID:2545646
Abstract

Our previous studies have shown that the aldose reductase inhibitor (ARI), sorbinil, prevents galactose-induced alterations and cataracts in rat lenses. We have now used sorbinil as well as another ARI, Eisai compound E-0722, to determine their potency in inhibiting aldose reductase- and galactose-induced alterations in lens morphology and Na+-K+-ATPase activity. Young Sprague Dawley rats were fed Purina Rat Chow plus 50% galactose, with or without 15 mg sorbinil, 0.15, 0.5 or 1.0 mg of E-0722/kg body weight per day. Controls were given Purina Rat Chow with or without ARIs. Lenses were studied for up to 60 days following the initiation of the diet using morphological, cytochemical and biochemical approaches to assess any alterations in the lens. While galactose-induced damage and cataracts were delayed by low doses (0.15 mg and 0.5 mg) of E-0722, they were completely prevented by the administration of 15 mg of sorbinil or 1 mg of E-0722/kg body weight per day. This study further showed that just 1 mg of E-0722 was more effective in preventing cataracts than 15 mg sorbinil. Thus it appeared that E-0722 was a more potent inhibitor of aldose reductase than sorbinil.

摘要

我们之前的研究表明,醛糖还原酶抑制剂(ARI)索比尼尔可预防半乳糖诱导的大鼠晶状体改变和白内障。我们现在使用索比尼尔以及另一种ARI依赛化合物E-0722,来确定它们在抑制醛糖还原酶和半乳糖诱导的晶状体形态改变及钠钾ATP酶活性方面的效力。将幼年斯普拉格-道利大鼠喂以普瑞纳大鼠饲料加50%半乳糖,每天给予或不给予15毫克索比尼尔、0.15、0.5或1.0毫克E-0722/千克体重。对照组给予含或不含ARI的普瑞纳大鼠饲料。在开始喂食后的60天内,使用形态学、细胞化学和生物化学方法研究晶状体,以评估晶状体的任何改变。虽然低剂量(0.15毫克和0.5毫克)的E-0722可延缓半乳糖诱导的损伤和白内障形成,但每天给予15毫克索比尼尔或1毫克E-0722/千克体重可完全预防。这项研究进一步表明,仅1毫克E-0722在预防白内障方面比15毫克索比尼尔更有效。因此,E-0722似乎是比索比尼尔更有效的醛糖还原酶抑制剂。

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