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)

Studies have been made of the effects of X-ray on various lens reducing systems, including the levels of NADPH and glutathione (GSH), the activity of the hexose monophosphate shunt (HMS) and of certain enzymes, including GSH reductase, GSH peroxidase, and glucose-6-phosphate dehydrogenase (G-6-PG). It was found that during several weeks following X-irradiation but prior to cataract formation, there was very little change in the number of reduced -SH groups per unit weight of lens protein but that, with the appearance of cataract, there was a sudden loss of protein -SH groups. In contrast, the concentration of GSH in the X-rayed lens decreased throughout the experimental period. Similarly, the concentration of NADPH in the X-rayed lens was found to decrease significantly relative to controls 1 week prior to cataract formation, and the ratio of NADPH to NADP+ in the lens shifted at this time period from a value greater than 1.0 in the control lens to less than 1.0 in the X-rayed lens. A corresponding decrease occurred in the activity of the HMS in X-rayed lenses as measured by culture in the presence of 1-14C-labeled glucose, G-6-PD was partially inactivated in the X-rayed lens. Of the eight enzymes studied, G-6-PD appeared to be the most sensitive to X-irradiation. The data indicate that X-irradiation results in a steady decrease in the effectiveness of lens reducing systems and that when these systems reach a critically low point, sudden oxidation of protein -SH groups and formation of high-molecular-weight protein aggregates may be initiated.
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PMID:The effects of X-irradiation on lens reducing systems. 3 84

Activities of catalase (H2O2: H2O2 oxidoreductase, EC 1.11.1.6) and GSH peroxidase (GSH: H202 oxidoreductase, EC 1.11.1.9) have been measured in iris, ciliary body, retina, corneal epithelium, corneal endothelium, lens capsule-epithelium and decapsulated lens. 3-Amino-1H-1,2,4-triazole is a specific inhibitor of catalase and a potent cataractogenic agent. We observed marked inhibition of catalase activity in these tissues 1--6 h after the administration of a single intravenous dose of 1 g 3-aminotriazole per kg body weight in rabbit. This was associated with a 2--3-fold increase in the H2O2 concentrations of aqueous humor and vitreous humor. The increased peroxide concentrations were restored to the physiological levels as the catalase activity of eye tissues gradually returned to normal with time after injection. Under the conditions, GSH peroxidase activity of the afore-mentioned eye tissues was unaltered, GSH and protein sulfhydryl of lens were not changed, and ascorbic acid of aqueous humor and vitreous humor was not significantly altered. Based on these findings our conclusion is that catalase of eye tissues regulates the endogenous H2O2 in eye humors to the physiological level. We speculate that H2O2 may be the triggering factor in cataract induced by 3-aminotriazole.
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PMID:Regulation of hydrogen peroxide in eye humors. Effect of 3-amino-1H-1,2,4-triazole on catalase and glutathione peroxidase of rabbit eye. 88 79

Nuclear cataract formed in rat lens in response to a protocol of multiple, low doses of sodium selenite. Nuclear cataract occurred, in both Wistar and Sprague-Dawley rats, following five subcutaneous injections of selenite over an 8-day period with an accumulated dose of 40-50 nmol selenite g-1 body weight. Glutathione content decreased within the first 24 hr of treatment and remained at 60% of controls. Lipid peroxidation occurred in Wistar rats prior to nuclear cataract formation. A two to three-fold increase in calcium concentration and decreased protein content accompanied nuclear cataract development. Enzyme activities were measured for glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and only the peroxidase activity remained constant through the period of cataract formation. This protocol resulted in nuclear cataracts similar in appearance to those observed with a single, acute dose of selenite. The opportunity to control the rate of selenite-dependent cataract formation allows further definition of precataractous events.
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PMID:Biochemical changes and cataract formation in lenses from rats receiving multiple, low doses of sodium selenite. 147 77

The ability of transparent and cataractous human, rabbit and mice lenses to metabolize hydrogen peroxide in the surrounding medium was evaluated. Using a chemiluminescence method in a system of luminol-horseradish peroxidase and a photometric technique, the temperature-dependent kinetics of H2O2 decomposition by lenses were measured. The ability of opaque human lenses to catalyze the decomposition of 10(-4) M H2O2 was significantly decreased. However, this was reversed by the addition of GSH to the incubation medium. Incubation of the mice lenses with the initial concentration H2O2 10(-4) M led to partial depletion of GSH in normal and cataractous lenses. Human cataractous lenses showed decreased activities of glutathione reductase, glutathione peroxidase (catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids), superoxide dismutase, but no signs of depletion in activities of catalase or glutathione peroxidase (utilizing H2O2). The findings indicated an impairment in peroxide metabolism of the mature cataractous lenses compared to normal lenses to be resulted from a deficiency of GSH. An oxidative stress induced by accumulation of lipid peroxidation products in the lens membranes during cataract progression could be considered as a primary cause of GSH deficiency and disturbance of the redox balance in the lens.
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PMID:Peroxide-metabolizing systems of the crystalline lens. 173 65

The effects of chronic ethylene oxide (EtO) inhalation on the lens glutathione redox cycle were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, glutathione reductase decreased significantly in the lens while glutathione peroxidase did not. Glutathione reductase activity decreased time dependently, by as much as 81% after 13 weeks. In spite of changes in the glutathione redox cycle, reduced and oxidized glutathione levels were not affected. Our results raise the possibility that EtO inhalation may produce a cataract via changes in the glutathione redox cycle.
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PMID:Effects of inhaled ethylene oxide on the lens glutathione redox cycle in rats. 178 43

This investigation compared the effects of two types of aldose reductase inhibitors on several biochemical parameters in naphthalene-induced cataract of the rat over a time span of 102 days of treatment. Feeding of naphthalene daily to brown Norway rats resulted in gradual, progressive development of zonular opacities. As compared to control animals, the values of soluble protein, soluble glutathione (total of oxidized plus reduced) and activities of glutathione peroxidase and glutathione reductase were decreased in rats fed either naphthalene or naphthalene + FK366, a carboxylic-acid-type aldose reductase inhibitor. In marked contrast, treatment with A11576, a hydantoin-type aldose reductase inhibitor, maintained the values of most parameters (with one exception) at levels that were similar to those of the controls, and all lenses remained clear. A decline of glutathione was noted in all naphthalene-fed rats, irrespective of whether these animals had been treated with an aldose reductase inhibitor. The great decrease of glutathione with A11576 suggests that this inhibitor acts at some step in naphthalene metabolism following formation of naphthalene epoxide.
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PMID:Naphthalene-induced cataract in the rat. II. Contrasting effects of two aldose reductase inhibitors on glutathione and glutathione redox enzymes. 178 59

This investigation examined many parameters during the course of early development of naphthalene-induced cataract in a time span of 0 to 79 days of treatment. Feeding naphthalene daily to Black-Hooded rats resulted in gradual progressive development of cataract. The first faint opacities were detectable after 7 days. Free soluble total glutathione (oxidized and reduced) of these lenses was shown to gradually decrease to a maximum loss of about 20%, a value reached by day 30 of treatment. No activity loss of either enzyme required for glutathione synthesis (gamma-glutamylcysteine synthetase or glutathione synthetase) was observed in homogenates of naphthalene versus control lenses. There was also neither impairment of [35S]-L-cystine uptake nor of [35S]-glutathione synthetic capacity in lenses cultured from rats after 12, 24 or 36 days of naphthalene feeding when compared to control lenses. Hence, glutathione loss cannot be explained by a damaged glutathione synthesis system. Progressive activity loss of glutathione peroxidase and glutathione reductase was observed. The loss of glutathione peroxidase activity was especially remarkable. Thus, the defense system against oxidative damage is impaired and may be a significant factor in naphthalene-induced cataract of the rat.
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PMID:Glutathione synthesis and glutathione redox pathways in naphthalene cataract of the rat. 196 27

Many reports have pointed out that oxidative damage and disturbances in antioxidant defense systems of the lenses may play an important role in the development of cataract. In the present study the activities of glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, catalase and the level of glutathione and lipid peroxides were measured in red blood cells of galactosaemic children with cataract and without cataract. Furthermore the serum antioxidant activity and the level of uric acid. ceruloplasmin and transferrin in serum were estimated. It was found that in red blood cells of galactosaemic children with cataract the activity of glutathione reductase was slightly lower than in a control age-matched group of children and in galactosaemic children without cataract. The increase of serum antioxidant activity in both groups of galactosaemic children was also observed. Probably it could be due to the increase of the level of ceruloplasmin. Except glutathione reductase activity no other differences were found in the investigated components of the antioxidant defense systems of red blood cells and serum between galactosaemic children with cataract and those without cataract. Therefore it seems that red blood cells and serum metabolism are no good reflections of disturbances in antioxidant defense mechanisms which may be involved in the cataract development in galactosaemic children.
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PMID:Red blood cells and serum antioxidant defense systems of galactosaemic children. 208 Sep 1

Hydrogen peroxide (H2O2), a relatively stable oxidant, is present at low concentrations in the normal eye and is found at elevated concentrations in some patients with maturity-onset cataract. Recently, this laboratory has shown that H2O2 concentrations at levels only slightly above normal physiologic levels cause single-strand breaks in DNA within cultured lens epithelial cells obtained from calf lenses. It is hypothesized that such damage may contribute to the onset of cataract. The major enzyme which metabolizes H2O2 at the concentrations found in the eye is glutathione peroxidase. Since older individuals may have reduced activities of this enzyme and other enzymes involved in oxidative defense, this laboratory is synthesizing low-molecular-weight glutathione peroxidase mimics. It is possible that development of such compounds may improve the capacity of the lens to withstand oxidative stress in vitro.
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PMID:Oxidation and aspects of ocular pathology. 240 87

While it is recognized that oxidation has a major role in the development of cataract, few compounds have been developed which effectively reduce the potential for oxidative insult. A major oxidant confronting the lens is H2O2. Few compounds capable of metabolizing H2O2 have been synthesized. This communication reports that a number of compounds with glutathione peroxidase activity have been developed. Some of these compounds are 10 fold more active than Ebselen, previously recognized as the synthetic compound with the greatest GSH peroxidase activity.
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PMID:The synthesis of glutathione peroxidase analogs. 248 81


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