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 (P < 0.01).
Ranirestat significantly (P < 0.01) inhibited rapid
cataract development;
epalrestat did not.
Ranirestat significantly reversed the MNCV decrease (40.7 ± 0.6 m/s) in SDT rats dose-dependently (P < 0.01).
Epalrestat also reversed the prevented MNCV decrease (P < 0.05).
Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 ± 0.10 nmol/g), which
ranirestat significantly suppressed dose-dependently, (P < 0.05, <0.01, and <0.01);
epalrestat did not.
Ranirestat prevents DN and
cataract;
epalrestat prevents DN only.