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.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|