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Journal of Diabetes Research
Volume 2013, Article ID 175901, 8 pages
http://dx.doi.org/10.1155/2013/175901
Research Article

Effects of Long-Term Treatment with Ranirestat, a Potent Aldose Reductase Inhibitor, on Diabetic Cataract and Neuropathy in Spontaneously Diabetic Torii Rats

1Department of Ophthalmology, Jichi Medical University, Saitama Medical Center, 1-847 Amanuma-cho, Omiya-ku, Saitama-shi 330-8503, Japan
2Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka 554-0022, Japan
3Department of Integrated Medicine I, Jichi Medical University, Saitama Medical Center, Saitama 330-8503, Japan
4Division of Metabolism, Endocrinology and Nutrition, University of Washington School of Medicine, Seattle, WA, USA

Received 22 December 2012; Accepted 29 January 2013

Academic Editor: Tomohiko Sasase

Copyright © 2013 Ayumi Ota et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN) in spontaneously diabetic Torii (SDT) rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg) or epalrestat (100 mg/kg) for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal) to 3 (mature cataract). The combined scores (0–6) from both lenses represented the total for each animal. DN was assessed by measuring the motor nerve conduction velocity (MNCV) in the sciatic nerve. Sorbitol and fructose levels were measured in the lens and sciatic nerve 40 weeks after diabetes onset. Cataracts developed more in untreated rats than normal rats ( ). Ranirestat significantly ( ) inhibited rapid cataract development; epalrestat did not. Ranirestat significantly reversed the MNCV decrease (40.7 ± 0.6 m/s) in SDT rats dose-dependently ( ). Epalrestat also reversed the prevented MNCV decrease ( ). Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 ± 0.10 nmol/g), which ranirestat significantly suppressed dose-dependently, ( , <0.01, and <0.01); epalrestat did not. Ranirestat prevents DN and cataract; epalrestat prevents DN only.