title: AL-1576, an aldose reductase inhibitor (ARI), did not prevent the decrease of norepinephrine turnover in diabetic rats.
abstract: ONO-2235 [(E)-3-carboxymethyl-5-[(2E)-2-methyl-3-phenyl-propenylidene]rhodanine], an ARI, was reported to prevent significantly the decrease of norepinephrine (NE) turnover in three tissues of streptozotocin (STZ)-diabetic rats (1). To examine whether the partial restoration of NE turnover by ONO-2235 is related to its ARI activity, the effect of another ARI, AL-1576 [spiro(2,7-difluoro-9H-fluoren-9, 4'-imidazoline)-2'5'-dione], on NE turnover in STZ rats was investigated. STZ caused an accumulation of sorbitol in the lens and decreased NE turnover in interscapular brown adipose tissue (IBAT), heart and pancreas. AL-1576 totally prevented the accumulation of sorbitol in the lens but had no effect on the decreased NE turnover in all three tissues. These results suggest that the partial prevention of NE turnover decrease by ONO-2235 may not have been mediated by its ARI activity.
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000494:pharmacology*; D006827:Hydantoins / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
chemical_list: D005449:Fluorenes; D006827:Hydantoins; C052241:imirestat; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D009638:Norepinephrine