Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Naphthalene feeding can result in cataract formation in rats and rabbits due to specific metabolites of naphthalene. The concomitant administration of the aldose reductase inhibitor Al1576 to naphthalene-fed rats was proven to prevent cataract formation. To determine whether this effect was directly linked to the ability of Al1576 to inhibit enzyme aldose reductase, a variety of structurally diverse aldose reductase inhibitors, including the carboxylic acids tolrestat, Ponalrestat, and FK366, and the spirohydantoins, sorbinil and Al1576, were investigated for their ability to inhibit naphthalene-induced cataracts. Brown Norway rats, administered naphthalene by gavage, were fed normal rat chow containing these aldose reductase inhibitors at levels known to inhibit sugar cataract formation. The lens changes in these rats were monitored over a 90-day period by portable slit-lamp microscopy and histologic study. Al1576 showed a dose-dependent reduction in naphthalene-induced cataract formation, with no naphthalene-associated deposits seen in toluidine blue-stained lens sections. Sorbinil also reduced lens changes, whereas tolrestat, Ponalrestat, and FK366 had no effect. These results suggest that inhibition of naphthalene-induced cataract formation by structurally diverse aldose reductase inhibitors was not linked to the inhibition of aldose reductase.
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PMID:Effect of aldose reductase inhibitors on naphthalene cataract formation in the rat. 190 36

Several recent studies with the sorbitol dehydrogenase inhibitors 4-[4-(N,N-dimethylsulfamoyl)-piperazino]-2-methylpyrimidine, SDH-1, and its active metabolite 4-[4-(N, N-dimethylsulfamoyl)piperazino]-2-hydroxymethylpyrimidine , SDH-2, suggest that inhibition of sorbitol dehydrogenase may be beneficial in delaying the onset of diabetic complications due to their ability to ameliorate redox changes associated with polyol metabolism. To compare the relative importance of sorbitol dehydrogenase versus aldose reductase inhibition on sugar cataract formation, cataract formation was monitored in 50% galactose-fed and diabetic rats treated with/without the sorbitol dehydrogenase inhibitors SDH-1 or SDH-2 or the aldose reductase inhibitors AL 1576 or Ponalrestat. For these studies, diabetes was induced in young 50 g rats with streptozotocin while galactosemia was produced by feeding a diet containing 50% galactose. Inhibitors were administered in the diet with the diet containing 0.06% (w/w) of the sorbitol dehydrogenase inhibitors or Ponalrestat, and 0.0125% (w/w) of AL 1576. Cataract formation was monitored by hand-held slit lamp and polyol levels were measured by gas chromatography. Sugar cataract formation was accelerated in diabetic rats treated with sorbitol dehydrogenase inhibitors while no difference in cataract formation was observed in galactose-fed rats treated with/without SDH inhibitors. Cataract formation was inhibited in both diabetic and galactosemic rats by either Ponalrestat or AL 1576. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalysed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.
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PMID:Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats. 973 86

Diabetes mellitus occurrence has been associated to the modification of the physiological levels of glucose and is often accompanied by several long-term complications, namely neuropathy, nephropathy, retinopathy, cataract, and cardiovascular. Aldose reductase (AR) is an enzyme of aldoketo reductase super-family that catalyzes the conversion of glucose to sorbitol in the polyol pathway of glucose metabolism. In this context, aldose reductase inhibitors (ARIs) have received much attention worldwide. Decreased sorbitol flux through polyol pathway by ARIs could be an emerging target for the management of major complications of diabetes. The present review article describes a brief overview of the role of aldose reductase in the diabetic complications, advances achieved on ARIs and their potential use in the treatment and management of the major diabetic complications such as cataract, retinopathy, neuropathy, nephropathy and cardiovascular. The ARIs developed vary structurally, and representative structural classes of ARIs include i) carboxylic acid derivatives (such as Epalrestat, Alrestatin, Zopalrestat, Zenarestat, Ponalrestat, Lidorestat, and Tolrestat), ii) spirohydantoins and related cyclic amides (such as Sorbinil, Minalrestat, and Fidarestat), and iii) phenolic derivatives (related to Benzopyran-4-one and Chalcone). Among these inhibitors, Epalrestat is the only commercially available inhibitor till date. In addition, some other ARIs such as Sorbinil and Ranirestat had been advanced into late stage of clinical trials and found to be safe for human use. The role of various natural ARIs in management of diabetic complications will be discussed. Adapting ARIs could prevent sepsis complications, prevent angiogenesis, ameliorate mild or asymptomatic diabetic cardiovascular autonomic neuropathy and appear to be a promising strategy for the treatment of endotoxemia and other ROS-induced inflammatory diseases. The role of ARIs in non-diabetic diseases will also be discussed.
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PMID:Updates on Aldose Reductase Inhibitors for Management of Diabetic Complications and Non-diabetic Diseases. 2634 93