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)

The possible effects of Quercetine, a potent inhibitor of aldose-reductase, on cataract formation and vascular permeability were investigated in streptozotocine-diabetic rats. Preliminary results after peroral administration of Quercetine did not allow to demonstrate a clear inhibitory effect on cataract formation.
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PMID:[Diabetic cataract and flavonoids (first results) (author's transl)]. 41 68

The evidence of sorbitol excess in the crystalline lens of alloxan-diabetic rats has led to anticipate the role of the enzyme aldose-reductase in the pathogenesis of the diabetic cataract. In addition, a number of experimental works have more recently shown the involvement of myoinositol deficiency, which probably results from the sorbitol accumulation. These metabolic pathways are most likely implicated in the pathogenesis of diabetic neuropathy and perhaps additionally in that of microangiopathy. The synthesis of several aldose-reductase inhibitors (AR inhibitors) confirmed experimentally these hypothesis. By reducing the activity of the enzyme aldose-reductase, these substances suppress the adverse metabolic consequences of polyol accumulation, myositol deficiency and dysfunction of the Na+/K+ ATPase dependent sodium activity. Although different experimentations showed that the AR inhibitors could prevent in animals the development of experimental cataract as well as the early functional or later anatomic abnormalities of the diabetic retinopathy and nephropathy, the clinical trials did not clearly support these experimental results in humans. On the other hand, the AR inhibitors were proved to exhibit some efficacy in the early stage of diabetic neuropathy and in incipient nephropathy where they delay the development of albustix positive proteinuria. However, the benefit of an early treatment with AR inhibitors should be confirmed by long term prospective studies, which could also assess the safety of these drugs in chronic administration.
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PMID:[Role of polyols in the development of diabetic complications. Value of aldose-reductase inhibitors]. 141 Aug 79

Lovastatin is an inhibitor of HMG-Co A reductase, a key enzyme in cholesterol biosynthesis. It is of therapeutic value in hypercholesterolemia type IIa and leads to decreased levels of low-density lipoproteins in serum. Treatment with high doses of lovastatin has been reported to induce cataract formation in dogs. The goal of the ongoing prospective clinical study is to evaluate whether cataract formation is caused in humans by therapeutic doses of lovastatin. So far 28 patients (average age 44 years) suffering from hypercholsterolemia have entered the study. Besides thorough slit-lamp investigations in all patients, best corrected visual acuity and contrast sensitivity for five different spatial frequencies were measured. A reduction in contrast sensitivity is a sensitive indicator for opacities of lens and cornea. During a mean follow-up of 37 weeks (range 5-62 weeks) with a mean total dose of 15 g (range 2-26 g), no cataract formation or decreased contrast sensitivity has so far been observed.
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PMID:[Absence of cataractogenic effect of lovastatin (Mevinacor) so far]. 175 25

Young beagle dogs were fed a 30% galactose diet, with or without the aldose reductase inhibitors sorbinil or M79175. Cataract formation was monitored by indirect ophthalmoscope and hand-held slit-lamp microscopy and documented by retroillumination photography. In these dogs, the first sign of cataract development was an accentuation of the anterior and posterior lens sutures (1 month after feeding), then the appearance of cortical vacuoles (3 months after feeding), and finally, the formation of predominantly equatorial cortical opacities toward the posterior cortices (4-6 months after feeding). After long-term galactose feeding, a progressive, irregular, clear zone formed at the cortical equatorial regions. Light microscopic examination of these lenses shows that the cataracts are osmotic, many of the lens fibers appear to be swollen or ruptured, and vacuoles are seen near the bow region. Moreover, these histologic changes were reduced in a dose-dependent manner in galactose-fed dogs concomitantly treated with the aldose reductase inhibitors sorbinil or M79175. The osmotic nature of these cataracts and the observation that their formation can be reduced in a dose-dependent manner by aldose reductase inhibitors are consistent with the concept that the aldose-reductase catalyzed formation of polar sugar alcohols (polyols) initiates sugar cataract formation in the dog.
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PMID:Progression of sugar cataract in the dog. 190 66

The relationship between red blood cell sorbitol content and diabetic complications (cataract, retinopathy, neuropathy, and nephropathy) was examined in 23 non-insulin-dependent diabetic (NIDD) patients. Sorbitol content was abnormally high in 21 cases out of 23 NIDD patients. Sorbitol content in the non-neuropathy group and neuropathy group was 47.3 +/- 11.9 and 59.6 +/- 23.6 nmol/gHb, respectively. In the non-cataract group and cataract group, it was 49.0 +/- 17.6 and 66.0 +/- 23.5 nmol/gHb, respectively. The contents in the Scott I group and Scott II + III group were 54.9 +/- 20.7 and 58.7 +/- 24.0 nmol/gHb, respectively. Sorbitol content in the non-nephropathy group and nephropathy group was 52.8 +/- 19.8 and 61.1 +/- 21.9 nmol/gHb, respectively. The possibility that glyceraldehyde reductase (GAR) and sorbitol dehydrogenase (SDH) levels in red blood cells are also useful indicators of the presence of diabetic complications is strongly suggested.
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PMID:Studies on clinical markers of diabetes mellitus. 6. Red blood cell sorbitol and diabetic complications. 213 94

The administration of high dosages of various hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors has resulted in the development of subcapsular lenticular opacities in dogs. While dogs receiving cataractogenic doses of HMG-CoA reductase inhibitors experienced profound decreases in circulating serum cholesterol concentrations (40-60% reductions in total serum cholesterol), a causal relationship between serum cholesterol lowering and cataractogenesis was not established. A strong relationship was demonstrated, however, between the systemic exposure to inhibitor (plasma drug levels) and the cataractogenic potential of the various compounds studied. Analysis of lenses from dogs chronically dosed with various HMG-CoA reductase inhibitors revealed the presence of low drug levels in the lens (less than 500 ng equivalents g-1), but no correlation was observed between the amount of drug associated with the lens after chronic treatment and cataract development. In addition, no abnormalities in cholesterol content or sterol composition were observed in clear and/or cataract containing lenses from dogs chronically dosed with HMG-CoA reductase inhibitors. The kinetics of drug appearance in the aqueous and lens cortex was assessed after doses of various HMG-CoA reductase inhibitors, and suggested somewhat higher but not statistically significant peak concentrations of inhibitor were achieved by compounds which produced a higher incidence of cataracts. These data have suggested that high doses of HMG-CoA reductase inhibitors may increase lenticular exposure to drug via the aqueous humor by producing a substantial systemic exposure to drug substance. This may result in an increased concentration of inhibitor in the outer cortical region of the lens where cholesterol synthesis is critical, thereby resulting in the development of opacities. The production of lenticular changes by a HMG-CoA reductase inhibitor of diverse chemical structure establishes, with reasonable assurance, that these lens changes are mechanism based (i.e. a product of the biochemical mechanism of action of this class of compounds). An extrapolation of these findings to patients receiving therapeutic dosages enables a favorable risk evaluation since the doses to be employed clinically are much lower and result in a far lower systemic exposure to drug substance.
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PMID:On the etiology of subcapsular lenticular opacities produced in dogs receiving HMG-CoA reductase inhibitors. 230 97

The activity levels of glyceraldehyde reductase, an aldose-reductase-like enzyme present in the erythrocyte, were determined in 104 subjects, who were divided into five groups--diabetics with retinopathy and cataract, diabetics with retinopathy and no cataract, diabetics with no retinopathy and no cataract, non-diabetics with senile cataract, and non-diabetic normal controls. Diabetics with retinopathy and cataract had significantly higher mean enzyme activity levels than normal control subjects (2.5 fold increase, p < 0.001); so had diabetics with retinopathy but no cataract (2 fold, p < 0.01) and patients with senile cataract (1.5 fold, p < 0.05). Juvenile diabetics had a significantly higher enzyme level than maturity onset diabetics. There was no significant difference in glyceraldehyde reductase between normal controls and diabetics without retinopathy or cataract, and no significant difference in polyol-dehydrogenase activity levels between any group studied. Enzyme activity did not correlate with age or glycosylated haemoglobin (HbA1c) levels. The increase in levels of erythrocyte glyceraldehyde reductase were due to increased amounts of active enzyme, rather than to elaboration of new kinetic pathways.
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PMID:Erythrocyte glyceraldehyde-reductase levels in diabetics with retinopathy and cataract. 610 47

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

We assayed ferricyanide reductase activity (one of NADH-dependent diaphorase activities) in the soluble and insoluble fractions of cataractous human lenses. Activity of this reductase in both the soluble and insoluble fractions tended to decrease in order of cortex > nucleus periphery > nucleus center, and it was suggested that a decrease of the reductase activity is closely correlated with lens protein aggregation, and to some extent associated with the development of nuclear sclerosis (coloration) and cortical cataract. Furthermore, insoluble fraction had very high specific activity per mg insoluble protein in cortex, and the activity decreased sharply with an increase in the level of insoluble protein. The reductase activity in the insoluble fraction may be also related to the metabolic activity of plasma membranes.
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PMID:Ferricyanide reductase activity in cataractous human lens. 888 84

Cataract remains the major cause of blindness worldwide and a common complication of diabetes. Polyol accumulation in the lens is associated with cataract formation. Here we present evidence for a novel pathway for xylitol production in the lens involving glucuronate metabolism. Xylitol can be produced in rat and bovine lens from glucose, via the enzymes myo-inositol-oxygen oxidoreductase, D-glucuronate reductase, L-gulonate NAD(+)-3-oxidoreductase and L-iditol-NAD(+)-5-oxidoreductase, which have been found in the mammalian lens for the first time. Glucuronate reductase has been purified and was inhibited by thiol quenching reagents. UDP-glucuronyl transferase is also present in mammalian lenses; this enzyme may be an anti-toxic defense mechanism in the lens.
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PMID:Accumulation of xylitol in the mammalian lens is related to glucuronate metabolism. 889 89


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