Effects of an aldose reductase inhibitor, 1-[(p-bromophenyl)-sulfonyl]hydantoin, on cataract formation and tissue polyol levels in galactosemic rats.

Abstract

1-[(p-Bromophenyl) sulfonyl] hydantoin (p-Br-PSH), an inhibitor of aldose reductase, was intubated once daily at a dose of 25 or 50 mg/kg into rats fed a 50% galactose diet. Cataract formation was decreased in rats dosed with p-Br-PSH at 50 mg/kg from the first day on galactose diet relative to untreated galactosemic rats (control rats). In the groups pretreated with p-Br-PSH for 10 d before the start of galactose diet feeding, subsequent treatment with the drug markedly delayed cataract formation. Treatment with p-Br-PSH at 50 mg/kg from the first day (day 0) on galactose diet produced a statistically significant though small (<11%) decrease in the lenticular galactitol level at day 5 and 9. These results suggest that the delay of cataract formation by treatment with p-Br-PSH is caused not only by the decrease in osmotic pressure resulting from reduction in the lenticular galactitol level but also by other unknown mechanisms. Treatment with p-Br-PSH at 50 mg/kg reduced galactitol accumulation by about 50% at day 5 and 9 in the sciatic nerve and by 26% at day 26 in the retina. The sciatic nerve myo-inositol level in control rats was decreased by 42% at day 9 compared with that of normal diet fed rats. The galactosemic rats treated with p-Br-PSH at 25 and 50 mg/kg showed increases (16 and 34%, respectively) in the sciatic nerve myo-inositol level. The importance of these findings for the treatment of diabetic complications is discussed.