Effect of a new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) on peripheral nerve disorders in streptozotocin-diabetic rats.
A new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) was administered orally to streptozotocin-diabetic rats (60 mg/kg IV) for 14 days and its effect on motor nerve conduction velocity studied. The compound significantly improved motor nerve conduction velocity of diabetic rats at a minimal dose of 10 mg . kg-1 . day-1 (treated 28.8 +/- 0.5 versus untreated 23.2 +/- 4.7 m/s, p less than 0.01). The sorbitol content of the sciatic nerve and red blood cells measured after 2 weeks was concomitantly reduced in ONO-2235-treated rats (sciatic nerve: 120 +/- 13 versus 595 +/- 146 nmol/g wet weight; red blood cell: 91 +/- 21 versus 165 +/- 39 nmol/g haemoglobin; p less than 0.01 in both 20 mg . kg-1 . day-1-treated versus untreated animals). These results suggest that sorbitol accumulation might contribute to the development of peripheral nerve dysfunction in acutely diabetic animals and the new aldose reductase inhibitor could be a potential drug for therapy of diabetic neuropathy.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004912:Erythrocytes / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012236:Rhodanine / Q000031:analogs & derivatives / Q000494:pharmacology*; D012584:Sciatic Nerve / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D007328:Insulin; D013844:Thiazoles; D053778:Thiazolidines; C038131:epalrestat; D013012:Sorbitol; D012236:Rhodanine; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase