Effects of novel hydantoin derivatives with aldose reductase inhibiting activity on galactose-induced cataract in rats.
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概要
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Effects of novel aldose reductase inhibitors, M16209 (1-(3-bromobenzo[b]furan-2-y!sulfonyl)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 <I>myo</I>-inositol and decrease in glutathione (GSH) content in lenses preceded the appearance of opacity. Remarkable increase in NADPH content and decrease in NADP<SUP>+</SUP> content, in addition to elevation of the ratio of Na<SUP>+</SUP>/K<SUP>+</SUP>, 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 <I>myo</I>-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.
- 公益社団法人 日本薬理学会の論文
著者
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Okuda Jun
Department of Cardiology, Yokohama City University Medical Center
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Kato Katsuaki
Department Of Materials Science And Chemical Engineering Faculty Of Engineering Shizuoka University
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MIZOTA Masahiro
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd.,
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Murakami Nobuya
Department Of Pharmacology Fuji Central Research Laboratory Mochida Pharmaceutical Co. Ltd.
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Ohta Masahiko
Department Of Chemistry And Biochemistry Graduate School Of Engineering Kyushu University
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Nakayama Kazuo
Department Of Electrical Engineering And Computer Science Nagoya University
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MIWA ICHITOMO
Department of Clinical Biochemistry, Faculty of Pharmaceutical Science, Meijo University
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OHTA Masahiko
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd
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MURAKAMI Kimihiro
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd
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OKUDA JUN
Department of Biochemistry, School of Medicine, Nagoya University
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MURAKAMI Nobuya
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd
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MIZOTA Masahiro
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd
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MIWA Ichitomo
Department of Clinical Biochemistry, Faculty of Pharmacy, Meijo University
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KATO Katsuaki
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd
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NAKAYAMA Kazuo
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd
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