Effects of a new aldose reductase inhibitor on various tissues in vitro

Abstract

A new aldose reductase inhibitor, ONO-2235 [(E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene] rhodanine], was found to possess a potent inhibitory activity of aldose reductase, partially purified from rat lens (IC50 = 1.0 X 10(-8) M) and human placenta (IC50 = 2.6 X 10(-8) M). Against rat lens aldose reductase, ONO-2235 exhibited uncompetitive inhibition as previously observed with 7-hydroxy-4-oxo-4H-chromen-2-carboxylic acid. Sorbitol accumulation in the isolated rat lenses, sciatic nerves and human erythrocytes were all effectively inhibited during incubation with high concentrations of glucose (28-50 mM) by ONO-2235 at a concentration of about 10(-6) M. Because the accumulation of sorbitol has been reported to play an etiological role in the development of diabetic complications, the results suggest that ONO-2235 may prove to be useful in preventing and improving some diabetic complications.