Abstract
Abstract: :
Purpose: : It is well established that the intralenticular accumulation of sorbitol initiates osmotic changes that start a biochemical cascade of events that result in sugar cataract formation and that aldose reductase inhibitors block the formation of these cataracts by inhibiting the intralenticular accumulation of sorbitol. The purpose of this study was to determine if sugar cataract formation can also be delayed by methods independent of inhibiting sorbitol accumulation. Methods: Two analogs of 4–[4–(N,N–dimethylsulfamoyl)piperazino]–2–methylpyrimidine were synthesized and their effect on cataract formation was examined by orally administering these agents to diabetic rats. Results: Neither synthesized analog displayed significant aldose reductase or sorbitol dehydrogenase inhibition; however, both analogs appeared to delay cataract formation in diabetic rats without reducing lens polyol formation or hyperglycemia – the major initiating factors of diabetic cataract formation. Conclusions: This study suggests that the progression of lens opacification in diabetic rats can be delayed independent of inhibiting sorbitol formation, the initiating source of cataract formation.
Keywords: cataract • drug toxicity/drug effects