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)

Levels of lens aldose reductase, aldehyde dehydrogenase activity, and erythrocyte NADPH-oxidising (or glyceraldehyde reductase) activity were determined in 17 diabetic and 16 nondiabetic patients undergoing cataract extraction. Lens aldose reductase and aldehyde dehydrogenase activities were significantly lower in diabetics than in nondiabetics. Both enzymes showed significant inverse correlations with grouped HbA1c and fasting blood glucose levels. By contrast, erythrocyte NADPH-oxidising activity showed a significant positive correlation with grouped HbA1C. It is suggested that a direct effect of the glycaemic status on the lens enzymes is masked by a loss of enzymes secondary to the development of cataract. It is not yet possible to say whether erythrocyte NADPH-oxidising activity can be used to monitor aldose reductase activity in the lens or other tissues in clinical trials of aldose reductase inhibitors.
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PMID:NADPH-oxidising activity in lens and erythrocytes in diabetic and nondiabetic patients with cataract. 641 39

Sorbitol, resulting from glucose metabolism through aldose reductase, may play a role in diabetic complications such as cataracts, neuropathy, and vasculopathy. Sulindac (Clinoril) and sorbinil, two inhibitors of aldose reductase, decreased sorbitol formation in cataract or nerve tissue incubated in high glucose TC-199 media. Sulindac, a widely used anti-rheumatic drug, may have clinical applications in preventing diabetic complications.
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PMID:Diabetic complications in lens and nerve and their prevention by sulindac or sorbinil: two novel aldose reductase inhibitors. 641 48

An increased prevalence of cataract is associated with diabetes. Biochemical studies of diabetic lenses have revealed a variety of metabolic abnormalities including changes in the levels of electrolytes, glutathione, nucleotides and sugars. Similar biochemical changes have also been observed in cataracts associated with galactosaemia, suggesting that these sugar cataracts have a common biochemical aetiology. The common biochemical factor found to initiate both types of sugar cataract is the formation of sugar alcohols (polyols) from either glucose or galactose by the enzyme aldose reductase (alditol: NADP+ 1-oxidoreductase, EC 1.1.1.21). Increased intracellular levels of these polar alcohols have a hyperosmotic effect which leads to lens fibre swelling, vacuole formation and subsequent opacification. The process of sugar cataract formation in animals can be prevented by inhibiting aldose reductase.
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PMID:Diabetic and galactosaemic cataracts. 643 98

The possible multiple effect of galactose diet and X-irradiation on cataract development in mice was investigated by scanning electron microscopy. X-ray cataracts were induced by maintaining animals either on a normal or 50% galactose diet. No detectable changes in lens morphology were seen in animals fed galactose alone compared with normal controls. 2 months after X-ray, less damage had occurred to the lenses of the galactose-fed animals compared to those on a normal diet. At 4 months after X-ray, animals on a normal diet developed mature cataracts, while in the galactose-fed animals they were delayed by 0.5-1.5 months. Suppression of the development of X-ray cataract by galactose feeding may be related to the ability of this sugar, which accumulates in mouse lens due to the low levels of aldose reductase, to act as a free radical scavenger.
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PMID:Scanning electron microscopy of X-ray-induced cataract in mice on normal and galactose diet. 666 60

Flavonoids are known as potent inhibitors of aldose reductase, an enzyme that may initiate cataract formation in diabetes. We have tested the inhibitory activity of new flavone derivatives on a homogenate of lens epithelium. Compounds which inhibited the enzyme activity by more than 50 percent at 10(-60) M were then tested on rat lenses perfused in a 0.027 M glucose solution. Our preliminary studies indicate that these new flavone derivatives can prevent or delay the formation of cataract in an in-vitro model.
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PMID:[Aldose-reductase inhibitors and cataract formation (author's transl)]. 677 30

Cataract formation in galactosemic rats was studied by ophthalmoscopy, slit-lamp biomicroscopy, and by light microscopy using plastic embedding with methacrylate. Untreated rats developed nuclear cataracts by 14 days and mature cataracts by 21 days. However, rats treated with the aldose reductase inhibitor sorbinil did not develop any cataractous change for up to 8 months of 50% galactose feeding and could not be distinguished from normal controls. This strongly suggests that aldose reductase is the common factor involved in the formation of sugar cataracts.
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PMID:Galactose cataract prevention with sorbinil, an aldose reductase inhibitor: a light microscopic study. 679 19

Aldose reductase (AR) has been purified from canine kidneys, and a monospecific antibody against the enzyme prepared. These antibodies were used in an immunohistochemical test to detect tissue sites of aldose reductase in the dog, a species known to develop diabetic lesions morphologically identical to those seen in diabetic patients. Using this method, the enzyme has been demonstrated in numerous cell types, including lens epithelium, aortic endothelium and smooth muscle, Schwann cells of peripheral nerves, and, in the kidney, interstitial cells and cells of Henle's loop and the collecting tubules. Many other cells and tissues, including capillaries throughout the body, lack immunoreactive aldose reductase. The distribution of the immunoreactive enzyme is compatible with a potential role of the enzyme in the aetiology of some complications of diabetes, namely cataract, neuropathy, macroangiopathy and renal papillary necrosis, but not the microvascular complications.
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PMID:Immunohistochemical distribution of aldose reductase. 681 8

Thirty flavones, four isoflavones and thirteen coumarins were tested as inhibitors of lens aldose reductase, which is believed to participate in the initiation of cataract formation in diabetes. Many were found to be potent inhibitors, and the two most potent ones were axillarin (5,7,3',4'-tetrahydroxy-3,6-dimethoxyflavone) and 6,3',4'-trihydroxy-5,7,8-trimethoxyflavone (LARI 1). These two flavones inhibited aldose reductase purified from rat lens with IC50 values of 2.6 X 10(8) and 3.6 X 10(8) M respectively. They also inhibited aldose reductase purified from bovine lens with IC50 values of 1.8 X 10(7) M. The potencies of the two compounds were superior to those of all the previously reported inhibitors of aldose reductase. Inhibition of rat and bovine lens aldose reductases by the two compounds was of a non-competitive type with DL-glyceraldehyde as the variable substrate. Some flavones including axillarin and LARI 1 were found to be poorly or scarcely inhibitory against several adeninenucleotide-requiring enzymes, which are involved in glycolysis and other metabolic reactions. These results obtained show that the two flavones have some features which may be required in clinically useful drugs for diabetic patients. All the potent inhibitors of the compounds tested had a flavone skeleton, one (or two free) hydroxyl(s) in ring C, and more than three hydroxyls (free or methylated) in ring A. The possible relationships of structures to inhibitory potencies of the compounds tested are discussed.
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PMID:Inhibition of aldose reductases from rat and bovine lenses by flavonoids. 681 71

Two monomeric NADPH enzymes from pig lens, an aldehyde reductase and an aldose reductase, have been characterized. The aldose reductase is obtained in a pure form. The aldehyde reductase, usually called hexonate dehydrogenase, is the same protein as that was recently isolated from pig liver [Branlant, G. and Biellmann, J.F. (1980) Eur. J. Biochem. 105, 611-621]. The aldose reductase is shown to have a number of properties in common with the aldehyde reductase, namely its physico-chemical properties, its tendency to be inhibited by quercitine derivatives and its substrate specificity. These two enzymes differ in their immunological properties. Only aldose reductase has a reactive Cys residue, localized in or near the substrate binding site. In contrast to that shown for aldehyde reductase [Branlant, G. et al. (1981) Eur. J. Biochem. 116, 505-512; Branlant, G. (1982) Eur. J. Biochem. 121, 407-411], no anion-recognition sites are in the substrate binding site of aldose reductase. The fact that also sugars are substrates for aldose reductase support the idea that this enzyme is implicated in the formation of sugar cataract as suggested by Kinoshita, J.H. et al. [J. Am. Med. Ass. 246, 257-261 (1981)]. Pig lens aldose reductase does not show homotropic cooperative effects with respect to either substrate or coenzyme.
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PMID:Properties of an aldose reductase from pig lens. Comparative studies of an aldehyde reductase from pig lens. 681 41

Sorbinil, a potent aldose reductase inhibitor, can effectively block the progression of a galactose cataract even though the cataractous process is well underway. The prevention of dulcitol accumulation by Sorbinil is just as effective in reversing the cataract as the removal of galactose from the diet. The progression and reversal of the cataract were followed by ophthalmoscopy and histology. The results also further support the concept that in galactosemia the cataract is not caused by the toxic effects of galactose per se but by the consequence of the aldose reductase reaction.
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PMID:Reversal of galactose cataract with Sorbinil in rats. 684 Oct 13


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