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)

1. Cataract formation in streptozotocin-induced diabetes in rats was reduced by approximately 85% when a diet rich in maize oil (300 g/kg diet) (fat diet) was given, thus confirming results of earlier studies. However, the concentration of sorbitol in the lens of diabetic animals remained high, the values for diabetic rats given the standard diet and the fat died being 65 and 40 mumol/g protein respectively. 2. With the standard diet, the fatty acid profile of the triglycerides of the epididymal fat pads was characterized by a greater relative proportion of saturated fatty acids for the diabetic animals compared to that for the normal animals. The fat diet moderated the tendency towards saturation in the diabetic animals. 3. The fat diet had other effects on the diabetic animals; these included a reduced mortality rate, increased body-weight, a decrease in the daily water intake, and in the daily urinary excretion of glucose and urea. 4. In the diabetic animals the fat diet had no effect on the specific activities in the liver of hexokinase (EC 2.7.1.1), glucokinase (EC 2.7.1.2), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40). However, the specific activity of glucose-6-phosphatase (EC 3.1.3.9) was reduced, while that of malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) was increased. The NAD+:NADH ratio, as calculated from liver pyruvate and lactate concentrations, tended to increase. 5. The results suggested that the fat diet moderated the long-term metabolic effects of diabetes.
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PMID:The effect of an unsaturated-fat diet on cataract formation in streptozotocin-induced diabetic rats. 13 11

Tocopherols and tocotrienols (vitamin E) and ascorbic acid (vitamin C) as well as the carotenoids react with free radicals, notably peroxyl radicals, and with singlet molecular oxygen (1O2), this being the basis of their function as antioxidants. RRR-alpha-tocopherol is the major peroxyl radical scavenger in biological lipid phases such as membranes or low-density lipoproteins (LDL). L-Ascorbate is present in aqueous compartments (e.g. cytosol, plasma, and other body fluids) and can reduce the tocopheroxyl radical; it also has a number of metabolically important cofactor functions in enzyme reactions, notably hydroxylations. Upon oxidation, these micronutrients need to be regenerated in the biological setting, hence the need for further coupling to nonradical reducing systems such as glutathione/glutathione disulfide, dihydrolipoate/lipoate, or NADPH/NADP+ and NADH/NAD+. Carotenoids, notably beta-carotene and lycopene as well as oxycarotenoids (e.g. zeaxanthin and lutein), exert antioxidant functions in lipid phases by free-radical or 1O2 quenching. There are pronounced differences in tissue carotenoid patterns, extending also to the distribution between the all-trans and various cis isomers of the respective carotenoids. Antioxidant functions are associated with lowering DNA damage, malignant transformation, and other parameters of cell damage in vitro as well as epidemiologically with lowered incidence of certain types of cancer and degenerative diseases, such as ischemic heart disease and cataract. They are of importance in the process of aging. Reactive oxygen species occur in tissues and cells and can damage DNA, proteins, carbohydrates, and lipids. These potentially deleterious reactions are controlled in part by antioxidants that eliminate prooxidants and scavenge free radicals. Their ability as antioxidants to quench radicals and 1O2 may explain some anticancer properties of the carotenoids independent of their provitamin A activity, but other functions may play a role as well. Tocopherols are the most abundant and efficient scavengers of peroxyl radicals in biological membranes. The water-soluble antioxidant vitamin C can reduce tocopheroxyl radicals directly or indirectly and thus support the antioxidant activity of vitamin E; such functions can be performed also by other appropriate reducing compounds such as glutathione (GSH) or dihydrolipoate. The biological efficacy of the antioxidants is also determined by their biokinetics.
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PMID:Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids. 144 60

Since most of the known factors that are associated with cataract formation are oxidative in nature, one would expect that a highly reductive environment might arrest or retard the progress of cataract formation. Reduced nucleotides, both NADH and NADPH, are potent reductants with a large negative redox potential of -320 mV. Lenses of certain species contain high levels of these nucleotides, presumably due to the presence of taxon specific crystallins. We have utilized this situation to investigate whether the levels of reduced pyridine nucleotides modulate photo-oxidative damage to the lens. We have monitored the time dependent loss of tryptophan fluorescence upon photodamage for lenses from guinea pig, rabbit and frog (Rana) that contain high levels of pyridine nucleotides and compared with the lenses from rat, Xenopus and a mutant strain of guinea pig that contain significantly lower amounts of these nucleotides. About 75% and 90% of the initial fluorescence intensity is lost in the case of rat and Xenopus lenses, respectively, after a total of 35 min exposure. Rabbit, guinea pig and frog lenses, under identical conditions, show only about 35-40% loss of the initial fluorescence. It appears that the lenses that contain high levels of reduced nucleotides are less susceptible to photodamage. The observed anti-oxidative role of reduced nucleotides in the lenses indicates the possibility of testing reductants (NADPH, NADH and their functional analogues) as potential candidates to therapeutically intervene in the process of cataractogenesis.
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PMID:Levels of reduced pyridine nucleotides and lens photodamage. 145 82

Conditions of oxidative stress may lead to cataract formation. Reaction of certain flavoproteins, the NADH: oxidoreductases, with different quinones is well known to form hydrogen-peroxide. This reaction was investigated to get more information on cataract induction by naphthalene and its quinone metabolites. Protein extracts from bovine lens cortex exhibit "diaphorase" activity, indicated as dye reduction in the presence of NADH and dichlorophenol-indophenol (DCPIP) or ferricyanide. Different redox cycling compounds are shown to be active in this "diaphorase" reaction by lens protein extract (LCE): Oxygen consumption can be detected in the presence of pyrroloquinoline quinone and juglone whereas 1,4-naphthoquinone, menadione and paraquat are no redox cyclists in this flavoprotein catalyzed reaction.
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PMID:Cataract induction by 1,2-naphthoquinone. I. Studies on the redox properties of bovine lens proteins. 187 11

Naphthalene cataract is probably due to peroxide production through naphthoquinone (NQ) redox cycling and/or glutathione conjugation. Both mechanisms yield losses of essential SH-groups in cristallins and are thus probably involved in protein modification finally visible as lens opacity. 1,2-Naphthoquinone produces H2O2 in the presence of either ascorbate, glutathione, NADH or--to a lesser extend--by homogenates of lens protein preparations. In the presence of 1,2-naphthoquinone and the above reductive additions, both, oxygen uptake and H2O2 formation can be observed. Reductive oxygen activation in these systems are diminuated by iodide in a concentration-dependent manner. Since maleimide-treated proteins are less capable to activate oxygen by 1,2-naphthoquinone, a direct oxygen activation by the interactions of 1,2-naphthoquinone with protein-SH is indicated. Catalysis of "diaphorase"-type (dia) enzymes via NADH--dia--1,2-NQ--O2 seems not to operate in hydrogenperoxide production during 1,2-naphthoquinone lens toxicity.
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PMID:Cataract induction by 1,2-naphthoquinone. II. Mechanism of hydrogenperoxide formation and inhibition by iodide. 187 12

The possibility that vitamin E or other antioxidants might prevent cataracts was tested by incubating rat lenses in vitro in galactose-enriched medium or by treating rats fed a diet containing 50% galactose (w/w). The vitamin E was added to the medium at 2.4 microM, and to the diet at a level of 5 g kg-1 diet. In vitro, lenses incubated with 55.6 mM galactose underwent globular degeneration, which was partially prevented by addition of vitamin E (2.4 microM). Even in such vitamin E-protected lenses, which appeared clear, many small globules could be seen in the region of interdigitation at the 'corners' where hexagonal cells intersected. In vivo, in dietary experiments, a dense nuclear opacity of the lens was observed after approximately 5 weeks; unlike diabetic cataracts, this was not prevented by the addition of vitamin E to the diet. The extensive globular degeneration observed was typical of that found in long-term (21-week diabetic) cataracts. Although no significant difference in cataract incidence was observed, the extent of damage in vitamin E-treated rat lenses appeared to be less. The difference in effectiveness of vitamin E in galactose-induced cataracts, as compared to diabetic cataracts, is tentatively ascribed to (1) the more severe osmotic stress expected from the products of the aldose reductase pathway for galactose and (2) the greater depletion of reduced pyridine nucleotides (NADPH + NADH) expected of galactose as compared to glucose.
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PMID:Modelling cortical cataractogenesis VII: Effects of vitamin E treatment on galactose-induced cataracts. 397 62

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

When 0.25 mumol of hydrocortisone succinate sodium (HC) was administered to 15-day-old hen's fertile eggs, almost all lenses of the embryos became cataractous with stages IV-V (> 90%) 48 h after the treatment. However, a triple application of propylene glycol (1.5 mmol/egg) at 3, 10 and 20 h after HC treatment effectively prevented the HC-induced cataract formation (I: 84%, II: 12%, III: 4%, IV-V: 0%) and repressed the decline of glutathione and the elevation of lipid peroxide in the lens caused by HC. Propylene glycol is metabolized to lactate and pyruvate producing NADH and is known to possess protective activities against X-ray irradiation. These properties have modified the HC-induced effects and decreased the production of oxidative stress in ovo, protecting the lens from losing its transparency after HC administration. Furthermore, a marked elevation of glucose in cataractous lenses noted after HC administration was not directly involved in opacification of the lenses.
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PMID:Glucocorticoid-induced cataract of the developing chick embryo-prevention by propylene glycol. 892 8

In diabetic cataract, sorbitol pathway flux perturbs intracellular metabolism by two putative mechanisms. The osmolyte hypothesis implicates the aldose reductase enzyme, increased rate of reduction of glucose of sorbitol and reciprocal osmoregulatory depletion of organic osmolytes (myo-inositol). Redox hypothesis favors alterations in the ratios (NADP+/NADPH and/or NADH/NAD+ as the primary cause of glucose-induced aldose reductase related defects. Increase in NADH/NAD+ promotes increased oxidation of sorbitol to fructose by polyol dehydrogenase; potential normalization of this ratio by coadministration of pyruvate (which reoxidizes NADH to NAD+ via lactate dehydrogenases reaction) was investigated. Effects of exogenous pyruvate on lens polyol formation and sodium-dependent myo-inositol (MI) cotransporter using two in vitro models of sugar cataract were determined. Rat lenses were incubated for 16 h in either normal (5.5 mM) or high sugar medium, 35.5 mM glucose or 30 mM galactose. Then lens MI influx was compared to polyol, MI and fructose content. Pyruvate did not affect MI influx or sorbitol content in lenses incubated in control medium. In 35.5 mM glucose, coadministration of pyruvate maintained lens MI influx at 76% of control values vs. 43% for lenses without pyruvate. Furthermore, pyruvate treatment diminished lens sorbitol content by 50% and increased lens sugar content (myo-inositol, fructose, lactate) and media lactate levels. Lenses incubated in high galactose medium formed galactitol with a corresponding decreased MI content. Coadministration of pyruvate had no effect on either lens sugar content (galactitol, myo-inositol, fructose) or MI influx, consistent with the fact that galactitol was not metabolized to fructose. In conclusion, pyruvate did not exert a direct effect on the MI co-transporter or prevent galactitol inhibition of MI influx. Coadministration of pyruvate with high glucose altered lens metabolism and promoted reduction of pyruvate to lactate, increased fructose, decreased sorbitol, enhanced MI influx, maintained lens MI content, implicating both osmotic and redox systems.
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PMID:Effect of pyruvate on lens myo-inositol transport and polyol formation in diabetic cataract. 932 7

The polyol pathway is one of the possible biochemical mechanisms by which hyperglycemia could impair the function and structure of the cells affected by diabetic complications. As possible hypothesis for the pathogenesis of diabetic complications, the polyol osmotic theory, alterations in myo-inositol and sodium metabolism, intermediary metabolites, abnormal changes of the redox state (NADH/NAD+ ratio) and an abnormality of kinase C dependent protein phosphorylation have been proposed. Recently, increasing evidence suggests that glycation and oxidative stress may have a cross-link with polyol pathway, contributing to the development of diabetic complications. If hyperglycemia-induced polyol pathway hyperactivity has an important role in the etiology of late-onset diabetic complications, the inhibition of aldose reductase (AR), a rate-limiting enzyme of the pathway, could become a key element in the prevention and reversal of diabetic complications. Recent evidence from both animal experiments and clinical studies has emerged to support this theory, resulting in the development of drugs available for the clinical treatment of diabetic neuropathy. From the results obtained mainly in animal models of diabetic complications, it is well recognized at present that AR inhibitors have a positive inhibitory effect on neuropathy, retinopathy, nephropathy, keratopathy, cataract-formation, possibly infection and atherosclerosis. It is now clear that AR inhibitors may offer various benefits to patients with diabetic complications. However, more extensive efforts are needed for the evaluation of their effects.
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PMID:New concepts and insights on pathogenesis and treatment of diabetic complications: polyol pathway and its inhibition. 948 Oct 88


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