Kato K, Nakayama K, Ohta M, Murakami N, Murakami K, Mizota M, Miwa I, Okuda J
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan.
Jpn J Pharmacol. 1990 Dec;54(4):355-64. doi: 10.1254/jjp.54.355.
Effects of novel aldose reductase inhibitors, M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) and M16287 (1-(3-chlorobenzo[b]furan-2-ylsulfonyl)hydantoin), on galactose-induced cataract formation in rats were investigated. Rats fed a 30% galactose diet developed lenticular opacity in the peripheral region by the 6th day of galactose feeding and showed gradual progression of opacity from the equator to the center of lenses. Histological study on the 15th day showed apparent lens fiber swelling and vacuolation predominantly in the equatorial and anterior cortical regions. Biochemical changes such as accumulation of galactitol, depletion of myo-inositol and decrease in glutathione (GSH) content in lenses preceded the appearance of opacity. Remarkable increase in NADPH content and decrease in NADP+ content, in addition to elevation of the ratio of Na+/K+, in lenses were also observed on the 15th day. Both M16209 and M16287 (10, 30 and 100 mg/kg/day, p.o.) dose-dependently ameliorated these morphological and biochemical changes except that restoration of myo-inositol content was incomplete. These results indicate that M16209 and M16287 can prevent galactose-induced cataract formation through amelioration of metabolic disorders and thus have high potential for clinical use in the treatment of some diabetic complications.
研究了新型醛糖还原酶抑制剂M16209（1-(3-溴苯并[b]呋喃-2-基磺酰基)乙内酰脲）和M16287（1-(3-氯苯并[b]呋喃-2-基磺酰基)乙内酰脲）对大鼠半乳糖诱导性白内障形成的影响。喂食30%半乳糖饮食的大鼠在喂食半乳糖第6天时，晶状体周边区域出现晶状体混浊，并显示混浊从赤道向晶状体中心逐渐进展。第15天的组织学研究显示，明显的晶状体纤维肿胀和空泡化主要发生在赤道和前皮质区域。在混浊出现之前，晶状体中就出现了一些生化变化，如半乳糖醇积累、肌醇消耗和谷胱甘肽（GSH）含量降低。第15天还观察到晶状体中NADPH含量显著增加、NADP+含量降低，以及Na+/K+比值升高。M16209和M16287（10、30和100mg/kg/天，口服）均剂量依赖性地改善了这些形态学和生化变化，但肌醇含量的恢复不完全。这些结果表明，M16209和M16287可通过改善代谢紊乱来预防半乳糖诱导性白内障的形成，因此在治疗某些糖尿病并发症方面具有很高的临床应用潜力。
