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)

Aldose reductase (AR) and sorbitol dehydrogenase (SDH) make up the sorbitol pathway, which has been implicated in the pathogenesis of sugar cataracts. The levels of the two enzymes were determined with quantitative histochemical techniques in the epithelium, cortex, and nucleus of normal and diabetic rat lenses. The ratio of activity of AR to SDH was found to be nearly 50 to 1 in all substructures. This would strongly favor sorbitol accumulation and subsequent cataract formation.
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PMID:Aldose reductase and sorbitol dehydrogenase distribution in substructures of normal and diabetic rat lens. 40 52

In addition to the already recognized metabolic diseases which have been associated with cataract formation, e.g. galactosaemia, galactokinase deficiency, Lowe's syndrome and diabetes, several other disorders can also lead to the development of cataracts. They are sorbitol dehydrogenase deficiency, uridine diphosphate galactose-4-epimerase deficiency, marginal maternal transferase and galactokinase deficiency, galactitol and sorbitol accumulation of unknown origin, heterozygosity for galactosaemia and galactokinase deficiency as well as the carrier state for Lowe's syndrome. In this review these metabolic disorders have been divided into five groups according to the age at the first appearance of lens clouding and the possible means of treatment have been discussed.
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PMID:Cataract and metabolic disease. 212 17

Galactitol and sorbitol concentrations in plasma were determined in patients (with or without cataract) in whom homo- or heterozygosity for galactokinase, galactose-1-phosphate uridyltransferase, systemic or peripheral UDP-galactose epimerase and sorbitol dehydrogenase deficiency was confirmed. For the above disorders it can be concluded that elevation of plasma polyols is not always related to the presence or absence of cataract. In all cases with cataract, however, the plasma galactitol or sorbitol levels were elevated. In another group of patients with unexplained congenital or infantile cataracts, but without apparent enzyme defects, mild to moderately elevated concentrations of plasma galactitol or sorbitol were found in about 45%. In 8% of this group the cataract and the elevated plasma galactitol concentration could possibly have been related to partial maternal enzyme deficiency. In all the other cases the elevated plasma polyol concentration remains unexplained but could indicate a further cause of cataract formation due to a hitherto unknown galactose or glucose metabolic aberration.
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PMID:Plasma polyol levels in patients with cataract. 212 18

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 pulse Fourier NMR was employed to measure the artificial diabetic cataract lens at various stages of its formation, and the lenses of the normal rats. Data obtained by using this method show that all the peaks that of water concentrate in the range of delta less than 4 ppm. The peak value at delta = 3.20 ppm is on a marked increase during the formation of cataract which is caused by the phosphate metabolites, such as GPC, ATP, ... etc, in cataract lens. With the development of the disease, the peak width at delta = 3.73 ppm becomes greater and greater, which shows that the activity of sorbitol dehydrogenase has decreased. This leads to a high concentration of the sorbitol in the cataract lens. Consequently, the osmosis pressure in the cataract lens is increased, and excessive water might dip into the crystalline lens to keep the balance of the osmosis pressure. And this might result in the hydration of the fiber cell of the crystalline lens, which might cause a swelling or blisters. These results are in favour of the prolongation of the relaxation time of cataractous lens reported in our other papers, and also support those gained by biochemical studies issued in the medical literature.
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PMID:[Detection of sorbitol content in crystalline lens of normal rats and rats with diabetic cataract by 1H-NMR]. 239 Oct 91

Sugar cataract formation has been demonstrated to result from lenticular sorbitol accumulation. In the lens, the activity of aldose reductase has been observed to increase with the onset of diabetes, while the activity of sorbitol dehydrogenase decreases. This shift in activities of these two Sorbitol Pathway enzymes favors the increased accumulation of sorbitol. Immunohistochemical studies with antibodies prepared against purified rat lens aldose reductase reveal a striking increase in immunoreactive positive staining for aldose reductase in lenses from diabetic rats. Two weeks after the onset of diabetes, increased immunohistochemical staining for aldose reductase appears beneath the epithelial region where water cleft formation occurs, and the intensity of this staining increases with the formation of vacuoles. By 6-8 weeks, the presence of large vacuoles and areas of liquifaction containing dense immunoreactive stain can be observed. Examination of human cataractous lenses with antibodies prepared against purified human placenta aldose reductase suggest similar increases in immunoreactive staining in the human diabetic lens. Cataractous lenses from diabetic patients revealed increased immunoreactive staining for aldose reductase, which was associated with the presence of vacuoles in both the anterior or posterior superficial cortical layers. Examination of similar vacuole containing regions from non-diabetic cataractous lenses revealed no increase in immunoreactive staining for aldose reductase. These results suggest that the enhanced activity of aldose reductase observed in diabetes is due to an increased amount of enzyme, rather than enzyme activation.
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PMID:Immunohistochemical localization for aldose reductase in diabetic lenses. 310 Apr 73

Polyhydric alcohols (polyols) are widely distributed in nature, and the enzymes of the polyol pathway (aldose reductase and sorbitol dehydrogenase) are present in many mammalian tissues. The function of this pathway remains a mystery. A primary role for the pathway in the pathogenesis of 'sugar cataract' was provided by a number of experimental observations and in the 1960s the 'osmotic hypothesis' was propounded. This hypothesis also had implications for the pathogenesis of diabetic neuropathy. However, in the 1970s doubts were raised about the validity of the hypothesis, culminating in experiments which suggested that abnormalities in myo-inositol metabolism in nerve and lens were more closely related to the glucose-induced functional changes in these tissues than was the polyol pathway. Nevertheless, increased activity of the polyol pathway must still be regarded as an instigator of the biochemical abnormalities that lead to damage of lens and nerve in diabetes mellitus.
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PMID:The polyol pathway. A historical review. 379 30

The novel compounds SDI 157 (2-methyl-4(4-N,N-dimethylaminosulfonyl-1-piperazino)pyrimid ine, CAS 131816-54-1) and SDI 158 (2-hydroxymethyl-4-(4-N,N-dimethylaminosulfonyl-1- piperazino) pyrimidine, CAS 140687-51-0) have been found to be inhibitors of sorbitol dehydrogenase. In normal and diabetic animals both compounds induced a dose-dependent increase of tissue sorbitol, especially in the peripheral nerve, without alteration of the blood glucose. In contrast to SDI 158, SDI 157 does not act in vitro. However, in the isolated perfused rat liver SDI 157 induced a high sorbitol release and plasma samples of animals treated with SDI 157 induced a sorbitol accumulation in vitro in erythrocytes like SDI 158. SDI 157 seems to be a prodrug. In accordance with the polyol theory, the chronic administration of SDI 157 to diabetic rats accelerated the cataract development and depleted the lens of total and oxidized glutathione. Surprisingly, however, it accelerated the motor nerve conduction velocity in normal and diabetic rats, normalized the glomerular filtration rate in diabetic rats and did not induce retinal capillary lesions in normal rats or aggravate those in diabetic rats. At single oral doses up to 100 mg/kg, SDI 157, was well tolerated by diabetic and normal rats. Except for a reduction of drinking water consumption, the chronic administration of SDI 157 in drinking water at doses up to 100 mg/kg per day had no side effects in normal, diabetic and galactoselfructose-rich diet rats.
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PMID:Sorbitol-accumulating pyrimidine derivatives. 798 40

In order to find an appropriate model of experimentally induced streptozotocin diabetic cataract rat for evaluation of the anti-cataract agents. Experimental diabetic cataracts were induced in 3 rat strains (Sprague-Dawley SD, Brown Norway BN, Wistar WIS), age 5 and 7 weeks old, by intravenous injection of 70 mg/kg streptozotocin. The cataract progression was followed by morphological and biochemical assessment. Two types of initial cataractous change were observed in SD and WIS rats which mainly consisted of water-vacuole formation in the peripheral area and a diffuse cloudiness progressing around the anterior Y-suture area. The initial change of BN rats was a Y-suture dissociation and fine water-clefts with dot-like vacuoles. Those initial changes in SD and WIS rats differed from those in BN. No difference in aldose reductase activities among the three strains was found, but BN rats had significantly higher sorbitol dehydrogenase activity than SD or WIS rats. It seems that 7-week-old BN rats are more suitable for experimental diabetic cataract models than SD or WIS.
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PMID:[Reinvestigation of streptozotocin induced diabetic cataract as a standard experimental model]. 831 49

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


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