Prevention of cataract development in severely galactosemic rats by the aldose reductase inhibitor, tolrestat.
With a fixed time period of galactose feeding, the rate of appearance of lenticular opacities depended on the severity of galactosemia, while with a fixed amount of galactose fed, the rate was time dependent. The capacity of tolrestat, a structurally novel inhibitor of aldose reductase (AR), to control cataract development was assessed in rats fed 30-50% galactose with the diet for 7 to 277 days. In rats fed 30% galactose for 31 days, the controlling effect of tolrestat was dose dependent, and no cataracts were detected at a dose of 35 mg/kg/day. In rats given tolrestat with the diet for 14 days, then rendered severely galactosemic with a diet containing 50% galactose, and subjected to continued treatment with tolrestat at a dose of 43 mg/kg/day, no changes were detected by slit-lamp microscopy after 207 days. The preventive effect was also dose dependent. In view of the established similarity in the pathogenesis of galactosemic and diabetic cataracts, the results obtained with tolrestat support its potential for controlling cataract development in diabetics.
D000818:Animals; D002386:Cataract / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004376:Galactitol / Q000032:analysis; D005690:Galactose / Q000494:pharmacology; D005693:Galactosemias / Q000150:complications*; D006801:Humans; D007908:Lens, Crystalline / Q000032:analysis / Q000187:drug effects; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats
D009281:Naphthalenes; C040550:tolrestat; D004376:Galactitol; D005690:Galactose