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 effect of several natural and synthetic compounds on selenite-induced cataract was investigated in rat pups. Simultaneous determination of glutathione S-transferase (GST), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT), superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were carried out in the lens, erythrocyte and plasma. The results showed that propolis, diclofenac, vitamin C (Vit-C) and quercetin prevented cataract formation to the extent of 70, 60, 58.4, and 40%, respectively. Standardized extract of Ginkgo biloba (Egb 761) did not affect the cataract formation. Selenite treatment caused a significant decrease in the activity of erythrocyte SOD. This was accompanied by a simultaneous increase in the levels of MDA either in lens and in plasma. A significant increase was shown in erythrocyte GST (substrate ethacrynic acid; eaa), and GPx activities and lens GST (substrate chlorodinitro benzene; cdnb) activity. Antioxidant treatment caused significant changes in enzyme activities and MDA levels. There was no effect of selenite and antioxidants on total body weight increase during the course of the study. Blood parameters did not correlate to lens parameters following selenite treatment. Our results suggest that antioxidant supplementation following selenite exposure may prevent the cataract formation and may enhance antioxidant defence of blood and lens.
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PMID:Effects of some probable antioxidants on selenite-induced cataract formation and oxidative stress-related parameters in rats. 1064 22

In a random trial 50 patients with unilateral/ bilateral idiopathic immature senile cataract (cortical n = 25, nuclear n = 25) requiring surgery at least in one eye were included in the present study. Reduced glutathione (GSH), vitamin E, malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were studied in these patients receiving either vitamin E (n = 12 in each subgroup) or placebo (n = 13 in each group) for 30 days. A comparable increase of vitamin E in both types of lens homogenates of cataractous patients was observed in the study group. The level of GSH in cortical cataractous lenses in the study group was significantly raised (p < 0.001) whereas it was not increased significantly in nuclear cataractous lenses (p > 0.05) as compared to the placebo group. The percentage decrease in MDA levels was greater in cortical cataracts (38.07%) than in the nuclear type (27.94%). The activity of GSH-Px in cortical lenses was higher than that in the nuclear cataractous lens. The change in the size of lens opacity in cortical cataractous patients receiving vitamin E therapy was significantly decreased as compared to the placebo group. There may be a direct modulating effect of vitamin E on some GSH-related enzymes and the cortex of the lens might be protected more than the nucleus.
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PMID:Protective function of alpha-tocopherol against the process of cataractogenesis in humans. 1074 28

The reducing compound glutathione (GSH) exists in an unusually high concentration in the lens where it functions as an essential antioxidant vital for maintenance of the tissue's transparency. In conjunction with an active glutathione redox cycle located in the lens epithelium and superficial cortex, GSH detoxifies potentially damaging oxidants such as H2O2 and dehydroascorbic acid. Recent studies have indicated an important hydroxyl radical-scavenging function for GSH in lens epithelial cells, independent of the cells' ability to detoxify H2O2. Depletion of GSH or inhibition of the redox cycle allows low levels of oxidant to damage lens epithelial targets such as Na/K-ATPase, certain cytoskeletal proteins and proteins associated with normal membrane permeability. The level of GSH in the nucleus of the lens is relatively low, particularly in the aging lens, and exactly how the compound travels from the epithelium to the central region of the organ is not known. Recently, a cortical/nuclear barrier to GSH migration in older human lenses was demonstrated by Sweeney et al. The relatively low ratio of GSH to protein -SH in the nucleus of the lens, combined with low activity of the glutathione redox cycle in this region, makes the nucleus especially vulnerable to oxidative stress, as has been demonstrated with use of in vivo experimental animal models such as hyperbaric oxygen, UVA light and the glutathione peroxidase knockout mouse. Effects observed in these models, which are currently being utilized to investigate the mechanism of formation of human senile nuclear cataract, include an increase in lens nuclear disulfide, damage to nuclear membranes and an increase in nuclear light scattering. A need exists for development of therapeutic agents to slow age-related loss of antioxidant activity in the nucleus of the human lens to delay the onset of cataract.
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PMID:Glutathione: a vital lens antioxidant. 1080 23

The high content of glutathione (GSH) in the lens is believed to protect the thiols in structural proteins and enzymes for proper biological functions. The lens has both biosynthetic and regenerating systems for GSH to maintain its large pool size (4-6 mM). However, we have observed that, in aging lenses or lenses under oxidative stress, the size of GSH pool is diminished; and some protein thiols are being S-thiolated by oxidized nonprotein thiols to form protein-thiol mixed disulfides, either as protein-S-S-glutathione (PSSG) or protein-S-S-cysteine (PSSC). We have shown in an H2O2-induced cataract model that PSSG formation precedes a cascade of events starting with protein disulfide crosslinks, protein solubility loss, and eventual lens opacification. Recently, we discovered that this early oxidative damage in protein thiols could be spontaneously reversed in H2O2 pretreated lenses if the oxidant was removed in time. This dethiolation process is likely mediated through a redox regulating enzyme, thioltransferase (TTase), which has been discovered recently in the lens. To understand if the role of oxidative defense and repair is the physiological function of TTase in the lens, we cloned the TTase gene and purified the recombinant human lens TTase. Although TTase required GSH for its activity, TTase was far more efficient in dethiolating lens proteins than GSH alone. It favored PSSG over PSSC and dethiolated gamma-crystallin-S-S-G better than the alpha-crystallin counterparts. Furthermore, TTase showed a remarkable resistance to oxidation (H2O2) in cultured rabbit lens epithelial cells when GSH peroxidase, GSH reductase, and glyceraldehyde-3-phosphate dehydrogenase were severely inactivated. We further showed that activity loss in those SH sensitive enzymes could be attributed to S-thiolation, but reactivation via dethiolation could be attributed to TTase. We conclude that TTase can regulate and repair the thiols in lens proteins and enzymes through its dethiolase activity, thus contributing to the maintenance of the function of the lens.
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PMID:Thiol regulation in the lens. 1080 24

Cataracts have been attributed to oxidative injury in proteins and lipids. Primary defenses that directly protect the lens against oxidative damage include small molecule antioxidants (vitamin C, vitamin E, glutathione and carotenoids) and antioxidant enzymes (superoxide dismutase, catalase, and the glutathione enzyme systems - glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase). In humans, low plasmatic levels of vitamin C, vitamin E and carotenoids have been associated with a high risk of senile cataracts. Dogs are more prone to develop cataracts. A decrease in antioxidant defenses could be responsible for increased lens oxidation and cataract development. In this study we report the levels of erythrocytic enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase) and plasma vitamin C as well as malondialdehyde, in normal and cataractous English Cocker Spaniel dogs. Plasma vitamin C levels were consistently lower in cataractous dogs (20.17 &mgr;M +/- 8.2 &mgr;M) when compared with normal dogs (24.1 &mgr;M +/- 9.4 &mgr;M). These results indicate a possibly decreased synthesis in vitamin C, leading to lower aqueous humor levels of this vitamin. Considering that vitamin C levels in the aqueous humor may be responsible for lens antioxidant maintenance, and that these levels are obtained from plasma secretion through the ciliary epithelium, decreased plasma levels may indicate a decrease in the antioxidant capacity of the aqueous humor.
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PMID:Antioxidant profile of cataractous English Cocker Spaniels. 1139 47

We have measured lipid peroxidation and the activity of antioxidant enzymes in lenses of alloxan injected rats. After 12 weeks alloxan treated rats developed lens cataract. Diabetes rats had both lower lens weight and lower level of proteins in soluble fraction of lens homogenate. Alloxan treatment is associated with a significant increase of thiobarbituric acid reactive substances and the activity of antioxidant enzymes superoxide dismutase and catalase. However, diabetes decreased the activity of glutathione peroxidase in rat lenses. These results show that alloxan, which changes antioxidant status in rat lenses, may cause complications associated with diabetes.
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PMID:Alloxan induced cataract in a rat. 1181 13

Cataract is the leading cause of blindness worldwide. It is a multifactorial disease primarily associated with oxidative stress produced by free radicals. The protection offered by various antioxidants in cataract development is well established. Polyphenolic compounds present in green tea (Camellia sinensis) are reported to possess antioxidant property in various pathological conditions. The present study was undertaken to evaluate the anticataract potential of green tea leaf (GTL) extract in the development of lens opacification. Enucleated rat lenses were randomly divided into normal, control and treated groups and incubated for 24 h at 37 degrees C. Oxidative stress was induced by sodium selenite in the culture medium of the two groups (except the normal group). The medium of the treated group was additionally supplemented with GTL extract. After incubation, lenses were subjected to glutathione and malondialdehyde estimation. Enzyme activity of superoxide dismutase, catalase and glutathione peroxidase was also measured in different sets of the experiment. In vivo cataract was induced in 9-day-old rat pups of both control and treated groups by a single subcutaneous injection of sodium selenite. The treated pups were injected GTL extract intraperitoneally prior to selenite challenge and continued for 2 consecutive days thereafter. Cataract incidence was evaluated on 16th postnatal day by slit lamp examination. There was positive modulation of biochemical parameters in the organ culture study. Green tea was also found to reduce the incidence of selenite cataract in vivo. The results suggest that green tea possesses significant anticataract potential and acts primarily by preserving the antioxidant defense system.
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PMID:Green tea (Camellia sinensis) protects against selenite-induced oxidative stress in experimental cataractogenesis. 1229

Recent studies show a relationship between oxidants, antioxidants, and degenerative disease of aging like cataract formation. Focal lens cortical changes and cortical liquification have been reported in patients with Down syndrome (DS) over 14 years. There is evidence supporting the hypothesis that trisomy 21 patients have an increase in free radical reactions. These changes in antioxidant system may play a role in cataractogenesis in Down syndrome. We screened serum samples from 12 patients with DS and cataract: and 12 healthy age and sex-matched persons. We evaluated the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) in erythrocytes. SOD and GSHPx levels of patients with DS were significantly higher than the control group. No significant changes were observed in GST and GSH levels between the DS and control groups. These findings suggest impairment in antioxidant system, which may be a possible mechanism for early cataract formation in DS.
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PMID:Antioxidant system in Down syndrome: a possible role in cataractogenesis. 1241 43

The high content of glutathione (GSH) in the lens is believed to protect thiols in structural proteins and enzymes for proper biological functions. The lens has both biosynthetic and regenerating systems for GSH to maintain its large pool size. However, ageing lenses or lenses under oxidative stress show an extensively diminished size of GSH pool with some protein thiols being S-thiolated by oxidized non-protein thiols to form protein-thiol mixed disulfides, either as protein-S-S-glutathione (PSSG) or protein-S-S-cysteine (PSSC) or protein-S-S-gamma-glutamylcysteine. It was shown in an H(2)O(2)-induced cataract model that PSSG formation precedes a cascade of events before cataract formation, starting with protein disulfide crosslinks, protein solubility loss and high molecular weight aggregation. Furthermore, this early oxidative damage in protein thiols can be spontaneously reversed in H(2)O(2) pretreated lenses if the oxidant is removed in time. This dethiolation process appears to have mediated through a redox-regulating enzyme, thioltransferase (TTase), which is ubiquitously present in microbial, plant and animal tissues, including the lens. The GSH-dependent, low molecular weight (11.8 kDa) cytosolic enzyme plays an important role in oxidative defense and can modulate key metabolic enzymes in the glycolytic pathway. The enzyme repairs oxidatively damaged proteins/enzymes through its unique catalytic site with a vicinal cysteine moiety, which can specifically dethiolate protein-S-S-glutathione and restore protein free SH groups for proper enzymatic or protein functions. Most importantly, it has been demonstrated that thioltransferase has a remarkable resistance to oxidation (H(2)O(2)) in cultured human and rabbit lens epithelial cells under oxidative stress conditions when other oxidation defense systems of GSH peroxidase and GSH reductase are severely inactivated. A second repair enzyme, thioredoxin (TRx), which is NADPH-dependent, is widely found in many lower and higher life forms of life. It can dethiolate protein disulfides and thus is an extremely important regulator for redox homeostasis in the cells. Thioredoxin has been recently found in the lens and has been shown to participate in the repair process of oxidatively damaged lens proteins/enzymes. These two enzymes may work synergistically to regulate and repair thiols in lens proteins and enzymes, keeping a balanced redox potential to maintain the function of the lens.
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PMID:Redox regulation in the lens. 1289 45

The role of nutritional supplementation in prevention of onset or progression of ocular disease is of interest to health care professionals and patients. The aim of this review is to identify those antioxidants most appropriate for inclusion in an ideal ocular nutritional supplement, suitable for those with a family history of glaucoma, cataract, or age-related macular disease, or lifestyle factors predisposing onset of these conditions, such as smoking, poor nutritional status, or high levels of sunlight exposure. It would also be suitable for those with early stages of age-related ocular disease. Literature searches were carried out on Web of Science and PubMed for articles relating to the use of nutrients in ocular disease. Those highlighted for possible inclusion were vitamins A, B, C and E, carotenoids beta-carotene, lutein, and zeaxanthin, minerals selenium and zinc, and the herb, Ginkgo biloba. Conflicting evidence is presented for vitamins A and E in prevention of ocular disease; these vitamins have roles in the production of rhodopsin and prevention of lipid peroxidation respectively. B vitamins have been linked with a reduced risk of cataract and studies have provided evidence supporting a protective role of vitamin C in cataract prevention. Beta-carotene is active in the prevention of free radical formation, but has been linked with an increased risk of lung cancer in smokers. Improvements in visual function in patients with age-related macular disease have been noted with lutein and zeaxanthin supplementation. Selenium has been linked with a reduced risk of cataract and activates the antioxidant enzyme glutathione peroxidase, protecting cell membranes from oxidative damage while zinc, although an essential component of antioxidant enzymes, has been highlighted for risk of adverse effects. As well as reducing platelet aggregation and increasing vasodilation, Gingko biloba has been linked with improvements in pre-existing field damage in some patients with normal tension glaucoma. We advocate that vitamins C and E, and lutein/zeaxanthin should be included in our theoretically ideal ocular nutritional supplement.
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PMID:An ideal ocular nutritional supplement? 1522 13


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