EFFECTS OF A NEW ALDOSE REDUCTASE INHIBITOR ON VARIOUS TISSUES INVITRO

  • 1 January 1984
    • journal article
    • research article
    • Vol. 229  (1) , 226-230
Abstract
A new aldose reductase inhibitor, ONO-2235 <BR(E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene] rhodanine}, possessed a potent inhibitory activity of aldose reductase, partially purified from rat lens (IC50 [median inhibitory concentration] = 1.0 .times. 10-8 M) and human placenta (IC50 = 2.6 .times. 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 was reported to play an etiological role in the development of diabetic complications, ONO-2235 may prove to be useful in preventing and improving some diabetic complications.