Intrinsic inhibition of aldose reductase

The development of aldose reductase inhibitors for the treatment of diabeti c complications, such as cataract and retinopathy, has been of intense inte rest in the pharmaceutical community for the last 20 years. To date, aldose reductase inhibitors have been synthetically developed from leads obtained from in vitro screening studies. Recently, we have observed that mammalian tissues contain intrinsic inhibitors of aldose reductase, which may be use d as potential drugs for treating diabetic complications with potentially l ess side effects than synthetic aldose reductase inhibitors. Intrinsic inhi bitor(s) of aldose reductase have been observed in the methanolic extracts from rat and human kidneys and bovine lenses that were subjected to a numbe r of chromatographic techniques, including counter current chromatography, flash chromatography, gel filtration and high pressure liquid chromatograph y. This inhibition results from a direct interaction between the inhibitor and enzyme. The intrinsic inhibitor, present in the lipophilic fraction of human kidney and bovine lens extracts, can easily penetrate into the lens t o inhibit sugar alcohol formation. Intraperitoneal injection of partially p urified bovine lens extract inhibited lens polyol formation in young rats f ed 50% galactose diet.