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)

We tried to counteract the appearance of galactosemic cataracts in weaned rats by high doses of vitamin E. Rats were fed a diet containing 33% galactose. Cataract development was monitored by biomicroscopy and by several biochemical parameters: K+/Na+ ratio, aldose reductase activity, level of protein and non-protein sulfhydryl (SH) groups. Vitamin E was given parenterally at a dose of 100 mg/kg/day. The K+/Na+ ratio drops after 15 days of galactosemia, while the level of the aldose reductase rises after only 5 days of treatment. The non-protein SH groups lens contents fall from the 5th day of treatment onwards, while protein SH groups are not affected. In short-term experiments vitamin E does not prevent biochemical changes caused by galactosemia. The oxidative insult does not seem to be primarily involved in galactose cataract.
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PMID:Changes of some biochemical parameters of the lens in galactose-treated weaned rats with and without vitamin E therapy. 392 May 97

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

A free radical mechanism of cataractogenesis involving enzymatic and nonenzymatic reactions, is proposed. Supporting experimental evidence is briefly reviewed. H2O2, which is one of the toxic metabolites of oxygen, was significantly increased 2-3 fold in ocular humors in several experimental cataracts and in human senile cataract. Various cataractogenic agents were also found to increase H2O2 in ocular humors in vivo prior to cataract formation. Enzymatic defenses against O2-. and H2O2 provided by superoxide dismutase, catalase and glutathione peroxidase were impaired in cataracts. In some cataracts, catalase and superoxide dismutase were affected earlier. Malondialdehyde (MDA), a major breakdown product of lipid peroxides was significantly increased by 2-4-fold in human senile cataract, in cataracts induced in rabbit and rat, and in hereditary cataracts in mice. All the reactive species of O2 (O2-., H2O2, OH. and 1 delta gO2) may participate in initiating lipid peroxidation of lens in vitro. Various scavengers of these species were capable of preventing lenticular lipid peroxidation, amongst which OH. scavengers were found to be the most effective. Biological antioxidant, vitamin E afforded 44% prevention of lipid peroxidation in lens. The important observation was that vitamin E was therapeutically effective in about 50% of animals in arresting cataract induced in rabbit by 3-aminotriazole. In these rabbits, H2O2 and ascorbic acid of ocular humors and MDA of lens were close to normal. It is our working hypothesis that the carbonyl groups of MDA and amino groups of amino acids, proteins, nucleic acids and their bases, and phospholipids could interact in a cross-linking reaction producing high molecular weight aggregates by Schiff-base conjugate formation in addition to disulfide cross-linking of proteins, and finally resulting in cataract.
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PMID:Molecular mechanism of cataractogenesis: III. Toxic metabolites of oxygen as initiators of lipid peroxidation and cataract. 631 86

Rat lenses incubated in tissue culture medium (M 199) maintain their transparency for a long period of time. The soluble corticosteroid, solumedrol (methyl prednisolone sodium succinate) was added to the medium, at concentrations including the range expected during rejection episodes following organ transplantation (3.8 X 10(-9) M-3.8 X 10(-6) M). At the lowest level used (3.8 X 10(-9) M), five lenses of 12 became opaque following a 48 hr incubation, while at higher concentrations of solumedrol almost all lenses developed opacities. Addition of vitamin E to the medium resulted in partial prevention of the cataract as judged by the smaller proportion of lenses becoming opaque. Examination of the lenses by scanning and transmission electron microscopy (SEM and TEM, respectively), indicated that in untreated lenses the initial location of the cataract is at the anterior pole of the lens where a deepening area of degeneration formed, followed by a uniform subcapsular layer of degeneration spreading over the remainder of the lens. Damage at this location is not typical of most in vitro cortical cataracts. In the presence of vitamin E the extent of damage was less, involving, initially, an equatorial wedge of globular degeneration and spreading anteriorly and posteriorly in a thinner subcapsular layer. This type of damage was more typical of that seen previously for cataracts induced by cytochalasin D, elevated glucose and hygromycin B.
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PMID:Modeling cortical cataractogenesis. V. Steroid cataracts induced by solumedrol partially prevented by vitamin E in vitro. 634

The mechanism of oxidative damage to the lens through intraocular photochemical generation of superoxide and its derivatization to other oxidants such as singlet oxygen, hydroxyl radical and hydrogen peroxide has been studied. Rat lenses when organ cultured aerobically in TC 199 containing additional amounts of riboflavin were damaged as demonstrated by an inhibition of the uptake of Rb 86 against a concentration gradient. The pump was not affected by light if the culture was conducted in the basal TC 199. However, light was observed to induce significant peroxidative degradation of the tissue lipids even in the basal medium, the degradation being indicated by the formation of malonaldehyde. Both the inhibition of the pump as well as the peroxidative degradation of the tissue lipids, were attenuated considerably by scavengers of superoxide and hydrogen peroxide. In addition, the lipid degradation was prevented by vitamins C and E. The results suggest that the photodynamic injury to the lens cation pump as well as to membrane lipids is incumbent upon an initial generation of superoxide and its derivatization to other oxidants. Thus, the ocular lens is susceptible to oxidative insult and physiological damage through photocatalytic generation of various oxygen radicals. Large concentrations of ascorbic acid in the aqueous humor seems to be able to provide significant protection against such an insult. Thus, this may be one of the functions of high concentration of ascorbic acid in the aqueous humor. The implication of oxidative stress has also been examined in the genesis of cataracts in vivo. Treatment with vitamin E of the Emory mouse led to a decrease in the rate of cataract progression suggesting that at least in some instances an oxidative stress could participate in the formation of cataracts. Oxygen radicals may inflict damage at multifarious biochemical sites. Human lens lipids were also shown to have an absorption maxima at 239 nm indicating their susceptibility to oxidative degradation. In addition the lipid extract has fluorescence similar to that of lipofuscins. The levels of MDA were higher in the brunescent cataracts as compared to that in the nonbrunescent cataracts. The implications of oxidative stress towards the genesis of cataracts in humans is being explored further.
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PMID:Oxidative stress on lens and cataract formation: role of light and oxygen. 636 May 40

Female rats were fed defined diets limiting in one or more of certain amino acids and with or without vitamin E throughout gestation and lactation. Deficits of tryptophan, phenylalanine/tyrosine, or methionine/cystine reduced the body weight of progeny to about 50% or less of normal but only low tryptophan was cataractogenic. When total dietary amino acids were 12.4%, a low (65 mg%) level of tryptophan resulted in 34% incidence of cataract if vitamin E was simultaneously withheld. Elevation of total amino acids to 24.8% while maintaining tryptophan at 65 mg% caused 70 or 90% incidence of nuclear lens opacities in the presence or absence, respectively, of vitamin E. Maternal dietary amino acid imbalance was also associated with a 50% decrease in lens insoluble (membrane) proteins in the progeny independent of dietary vitamin E or the occurrence of opacities.
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PMID:Cataract formation following limited amino acid intake during gestation and lactation. 646 60

Eye lens cataract is a late effect of exposure to ionizing radiation. Depending on the dose and quality of radiation impinging on the lens, the development of a clinically discernible cataract usually takes several months in animal models, when the lens is irradiated in situ. However, we have developed a rapid in vitro assay with the isolated intact rat lens to study the effect of radiation and influence of antioxidants as protective agents. After only 24 hr of post-irradiation incubation at 35.5 degrees C in complete medium 199 + 10% foetal calf serum, damage in the form of globular degeneration subcapsularly and 'holes' in the cortical fibre cells is detectable. Doses as low as 0.10 Gy seem to be capable of causing some damage, and vitamin E (2.4 microns) in the medium confers some protection to the irradiated lens.
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PMID:Radiation cataract formation diminished by vitamin E in rat lenses in vitro. 685 39

alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.
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PMID:alpha-Lipoic acid as a biological antioxidant. 764 94

Among aging disabilities, the one associated with the progressive decline of vision is functionally most disadvantageous. Cataracts are one of the more common causes of such visual disability. Several predisposing factors have been identified in the genesis of this disease. While it is perhaps a multifactorial process, significant developments have taken place in recent years suggesting that oxygen radicals are involved in the development of this aging manifestation. Antioxidant enzymes, such as catalase and superoxide dismutase, have been demonstrated to protect the lens cell membrane from oxidative stress as reflected by the prevention of the Na(+)-K(+)-ATPase-dependent pump deterioration due to oxyradical-dependent oxidation of its proteins and lipids. From the nutritional point of view, antioxidants such as ascorbate and vitamin E also offer significant protection to the lens against damage due to oxidative stress. Evidence regarding the protective effect of these nutrients has been based on lens organ culture studies in the presence of active oxygen, generated photochemically as well as enzymatically. The experiment involving photochemical environs simulate the status of the eye during the photopic vision. In vivo, the effectiveness of ascorbate against cataracts has been tested in rat pups developing cataracts under the oxidative influence of sodium selenite. Certain antioxidants produced metabolically also may be useful in protecting against cataracts. Pyruvate produced in glucose metabolism seems to be an important antioxidant. The efficacy of this compound has been tested within in vitro organ culture as well as in vivo, the latter experiments being done with selenite-treated rats. There is a hope that these and other nutritional and metabolic antioxidants may one day be useful in delaying or even preventing cataract formation in human beings.
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PMID:Prevention of cataracts by nutritional and metabolic antioxidants. 774 71

We investigated the effect of alpha-lipoic acid, a powerful antioxidant, on cataract formation in L-buthionine(S,R)-sulfoximine (BSO)-treated newborn rats and found that a dose of 25 mg/kg b.w. protected 60% of animals from cataract formation. L-buthionine(S,R)-sulfoximine is an inhibitor of glutathione synthesis, whose administration to newborn animals leads to the development of cataracts; this is a potential model for studying the role of therapeutic antioxidants in protecting animals from cataract formation. Major biochemical changes in the lens associated with the protective effect of alpha-lipoic acid were increases in glutathione, ascorbate, and vitamin E levels, loss of which are effects of BSO administration. Treatment with alpha-lipoic acid also restored the activities of glutathione peroxidase, catalase, and ascorbate free radical reductase in lenses of L-buthionine(S,R)-sulfoximine-treated animals but did not affect glutathione reductase or superoxide dismutase activity. We conclude that alpha-lipoic acid may take over some of the functions of glutathione (e.g., maintaining the higher level of ascorbate, indirect participation in vitamin E recycling); the increase of glutathione level in lens tissue mediated by lipoate could be also due to a direct protection of protein thiols. Thus, alpha-lipoic acid could be of potential therapeutic use in preventing cataracts and their complications.
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PMID:Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats. 775 Aug 5


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