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)

Apart from genetically programmed cell aging, different external aggressors related to oxidative stress and lipid peroxidation (LPO) can accelerate the skin aging phenomenon. Oxidative stress associated with the formation of lipid peroxides is suggested to contribute to pathological processes in aging and systemic diseases known as the risk factors for cataract. Despite the fact that L-carnosine-related peptidomimetics N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) (NAC) and carcinine (beta-alanylhistamine) are metabolically related to L-carnosine and have been demonstrated to occur in tissues of many vertebrates, including humans, these compounds were shown resistant toward enzymatic hydrolysis. A series of related biocompatible imidazole-containing peptidomimetics were synthesized in order to confer resistance to enzymatic hydrolysis and ex vivo improvement of protective antioxidative properties related to L-carnosine. The included findings revealed a greater role of N-acetylcarnosine (NAC) and carcinine ex vivo in the prolongation and potentiation of physiological responses to the therapeutical and cosmetics treatments with L-carnosine as antioxidant. 3-D molecular conformation studies proposed the antioxidant activity of peptidomimetics (carcinine, L-prolylhistamine, N-acetylcarnosine, L-carnosine) for metal ion binding, quenching of a number free radicals, and binding of hydroperoxide or aldehyde (including dialdehyde LPO products) in an imidazole-peroxide adducts. NAC can act as a time release (carrier) stable version of L-carnosine during application in ophthalmic pharmaceutical and cosmetics formulations which include lubricants. Carcinine, L-prolylhistamine show efficient deactivation of lipid hydroperoxides monitored by HPLC and protection of membrane phospholipids and water soluble proteins from the lipid peroxides-induced damages. This activity is superior over the lipophilic antioxidant vitamin E. The biologically significant applications of carnosine mimetics were patented by Dr. Babizhayev and the alliance Groups (WO 2004/028536 A1; WO 94/19325; WO 95/12581; WO 2004/064866 A1).
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PMID:Biological activities of the natural imidazole-containing peptidomimetics n-acetylcarnosine, carcinine and L-carnosine in ophthalmic and skin care products. 1638 26

Natural dietary ingredients are known for their antioxidant activity. Of such, curcumin, the active principle of turmeric, at 0.01% in the diet proved as pro-oxidative in galactose-induced cataract in vivo. The purpose of this study was to investigate the effect of vitamin E (VE), a well-known antioxidant, in combination with curcumin on the onset and maturation of galactose induced cataract. Periodic slit-lamp microscope examination indicated that in combination with vitamin-E, 0.01% curcumin (G-IV) delayed the onset and maturation of galactose-induced cataract. Biochemical analyses revealed that combined treatment of 0.01% curcumin and vitamin-E diet exhibited an efficient antioxidant effect, as it inhibited lipid peroxidation and contributed to a distinct rise in reduced glutathione content. The results indicate that natural dietary ingredients are effective in combination rather than the individual administration as they are complementing each other in reducing the risk of galactose induced cataract.
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PMID:Cumulative antioxidant defense against oxidative challenge in galactose-induced cataractogenesis in Wistar rats. 1699 28

The prevalence and effects of age-related macular degeneration (AMD) and cataract are increasing dramatically as the proportion of elderly in our population continues to rise. A multivitamin-multimineral supplement with a combination of vitamin C, vitamin E, beta-carotene, and zinc (with cupric oxide) is recommended for AMD but not cataract. Weak support exists for multivitamins or other vitamin supplements from observational studies of cataract. The results of observational studies suggest that a healthy lifestyle with a diet containing foods rich in antioxidants, particularly lutein and zeaxanthin, as well as n-3 fatty acids, appears beneficial for AMD and possibly cataract. The Age-Related Eye Disease Study II will evaluate some of these additional nutrients as dietary supplements in a randomized trial.
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PMID:Multivitamin-multimineral supplements and eye disease: age-related macular degeneration and cataract. 1720 15

This paper reviews recent findings on the implication of nutritional and genetic factors in age-related eye diseases: age-related macular degeneration (AMD; a degenerative disease of the retina) and cataract (opacification of the lens). Because of direct exposure to light, the eye is particularly sensitive to oxidative stress. Antioxidants, such as vitamin E, C or zinc, clearly have a protective effect in AMD and probably in cataract. In addition, two carotenoids, lutein and zeaxanthin, may play a more specific role in the eye: they accumulate in the retina, where they form the macular pigment, and in the lens. Their role is probably to filter out phototoxic blue light and to quench singlet oxygen. Finally, docosahexaenoic acid (an omega-3 polyunsaturated fatty acid) is particularly important for the retina, where it exerts structural, functional and protective actions. Besides, these diseases are strongly influenced by genetics, as demonstrated by familial and twin studies. The apolipoprotein E4 allele is associated with a reduced risk of AMD, while an association of AMD with complement factor H polymorphism has recently been demonstrated. Nutrigenomics, by studying the interactions between genetic variability and nutritional factors, represents a new challenge in order to account for interindividual variations in disease susceptibility. Such potential interactions are presented.
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PMID:Application of nutrigenomics in eye health. 1768 13

Diabetes is a major contributing factor in cataract development. In animal models where cataracts develop within days or weeks of diabetes it is well established that osmotic stress from the accumulation of sorbitol leads to cataract development. This mechanism might explain the rare cases of acute cataract sometimes found in patients with uncontrolled sustained hyperglycemia but cannot account for the vast majority of cataracts that developed after years of diabetes. Thus, a model that can simulate diabetic slow-developing cataract is needed. The contribution of osmotic and oxidative stress in cataract development in sorbitol dehydrogenase (SDH) deficient mice, a model for slow-developing cataract in diabetic patients was determined. Contribution of osmotic stress was assessed by HPLC measurement of sorbitol and by observing the effect of blocking sorbitol accumulation by aldose reductase (AR) null mutation in the SDH deficient mice. Contribution of oxidative stress was assessed by observing the effect of vitamin E treatment and the effect of null mutation of glutathione peroxidase-1 (Gpx-1) on cataract development in these mice. Lenticular sorbitol level was significantly increased in the SDH deficient mice, and blocking sorbitol accumulation by the AR null mutation prevented cataract development, demonstrating the contribution of osmotic stress in cataract development. SDH deficiency did not affect lens oxidative stress status. However, treatment with vitamin E significantly reduced the incidence of cataract, and Gpx-1 deficiency exacerbated cataract development in these mice. Our findings suggest that chronic oxidative stress impaired the osmoregulatory mechanism of the lens. This was not evident until modest increases in lens sorbitol increased the demand of its osmoregulatory function. This osmoregulatory dysfunction model is supported by the fact that the activity of Na+/K+-ATPase, the key regulator of cellular ions and water balance, was dramatically reduced in the precataractous lenses of the SDH deficient mice, and that treatment with vitamin E prevented the loss of Na+/K+-ATPase activity. This osmoregulatory dysfunction model might explain why diabetic patients who control their blood glucose moderately well are still susceptible to develop cataract.
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PMID:Synergistic effect of osmotic and oxidative stress in slow-developing cataract formation. 1876 Feb 74

The use of multivitamin-mineral supplements has become increasingly common, but whether the use of such supplements improves micronutrient status remains still unclear. The objective of this report is to investigate how a long-term vitamin-mineral supplementation following the US Recommended Daily Intake (RDI) affected the plasma levels of selected nutrients in a subset (No. = 407) of participants in the Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS). The CTNS was a double-blind, single centre, controlled clinical trial of 1020 participants aged 55-75 years randomized to a daily tablet of Centrum(R) or placebo. A representative sample of 40% of the 1020 subjects, whom plasma level of selected vitamins was determined at the baseline, was retested throughout the treatment period that averaged 9.0 +/- 2.4 years. Participants assigned to Centrum(R) showed a significant increase (p < 0.005) in mean/median plasma levels of vitamin E, beta-carotene, folate, and vitamin B12, and an improved riboflavin status when compared with participants assigned to placebo. Differences concerning vitamin C were statistically less relevant and those concerning vitamin A were at a borderline level. In the treated group the effect of supplementation on plasma levels of vitamins A, E, and C, and on the glutathione reductase activation coefficient was significantly higher in participants with lower nutritional status at baseline.
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PMID:Effects of multivitamin/mineral supplementation on plasma levels of nutrients. Report No. 4 of the Italian-American clinical trial of nutritional supplements and age-related cataract. 1963 63

Analogues of N,N-dimethyl-4-(pyrimidin-2-yl)piperazine-1-sulfonamide possessing a free radical scavenger group (FRS), chelating groups (CHL), or both (FRS + CHL) have been synthesized. Electrospray ionization mass spectrometry studies indicate that select members of this series bind ions in the relative order of Cu(1+) = Cu(2+) > Fe(2+) = Fe(3+) > Zn(2+) with no binding of Ca(2+) or Mg(2+) observed. In vitro evaluation of these compounds in human lens epithelial, human retinal pigmented epithelial, and human hippocampal astrocyte cell lines indicates that all analogues possessing the FRS group as well as the water-soluble vitamin E analogue 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid protect these cells against decreased cell viability and glutathione levels induced by hydrogen peroxide. In addition, those compounds possessing CHL groups also protected these cells against hydroxyl radicals generated by the Fenton reaction. These compounds are good candidates for the preventive treatment of cataract, age-related macular degeneration (AMD), and Alzheimer's dementia (AD).
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PMID:Multifunctional antioxidants for the treatment of age-related diseases. 2007 5

Abstract The present study was undertaken to investigate the ability of dietary supplements to reduce the formation and severity of cataracts in mice irradiated with high-energy protons or iron ions, which are important components of the radiation encountered by astronauts during space travel. The mice were exposed to proton or iron-ion radiation and fed with a control diet or diets supplemented with the soybean-derived protease inhibitor, Bowman-Birk inhibitor (BBI), in the form of BBI Concentrate (BBIC) or an antioxidant formulation [containing l-selenomethionine (SeM), N-acetyl cysteine (NAC), ascorbic acid, co-enzyme Q10, alpha-lipoic acid and vitamin E succinate] both before and after the radiation exposure. At approximately 2 years after the radiation exposure, the animals were killed humanely and lenses were harvested and characterized using an established classification system that assigns discrete scores based on the severity of the lens opacifications. The results showed that exposure to 1 GeV/nucleon proton (3 Gy) or iron-ion (50 cGy) radiation significantly increased the cataract prevalence and severity in CBA/J mice to levels above the baseline levels of age-induced cataract formation in this mouse strain. Treatment with BBIC or the antioxidant formulation significantly reduced the prevalence and severity of the lens opacifications in the mice exposed to iron-ion radiation. Treatment with BBIC or the antioxidant formulation also decreased the severity of the lens opacifications in the mice exposed to proton radiation; however, the decrease did not reach statistical significance. These results indicate that BBIC and the antioxidant formulation evaluated in this study could be useful for protecting astronauts against space radiation-induced cataracts during or after long-term manned space missions.
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PMID:Dietary supplements reduce the cataractogenic potential of proton and HZE-particle radiation in mice. 2019 20

Cataract, opacification of the lens, is one of the commonest causes of loss of useful vision during aging, with an estimated 16 million people world-wide affected. The role of nutritional supplementation in prevention of onset or progression of ocular disease is of interest to health care professionals and patients. The aging eye seems to be at considerable risk from oxidative stress. This review outlines the potential role of the new nutritional strategy on redox balance in age-related eye diseases and detail how the synergism and interaction of imidazole-containing amino acid-based compounds (nonhydrolized L-carnosine, histidine), chaperone agents (such as, L-carnosine, D-pantethine), glutathione-boosting agents (N-acetylcysteine, vitamin E, methionine), and N-acetylcarnosine eye drops plays key roles in the function and maintenance of the redox systems in the aging eye and in the treatment of human cataract disease. A novel patented oral health supplement is presented which enhances the anticataract activity of eye drops and activates functional visual acuity. The clinical data demonstrate the effectiveness and safety of a combined oral health care treatment with amino acids possessing chaperone-like activity with N-acetylcarnosine lubricant eye drops. L-carnosine and N-acetylcarnosine protected the chaperone activity of alpha-crystallin and reduced the increased posttranslational modifications of lens proteins. Biological activities of the nonhydrolyzed carnosine in the oral formulation are based on its antioxidant and antiglycating (transglycating) action that, in addition to heavy metal chelation and pH-buffering ability, makes carnosine an essential factor for preventing sight-threatening eye disorders having oxidative stress in their pathogenesis, neurodegeneration, and accumulation of senile features. The findings suggest that synergism is required between carnosine or other imidazole-containing compounds and reduced glutathione in tissues and cells for efficacious protection from protein carbonylation as a biomarker for the ability of the non-toxic compounds to reduce oxidative stress. Potential therapeutic applications of oral forms of nonhydrolized carnosine and their specific mechanisms to manage telomere attrition and vascular aging might help elderly patients to withstand the problems of sight-threatening eye diseases related to oxidative stress and accelerated biological ageing in linked with earlier onset of diseases.
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PMID:New concept in nutrition for the maintenance of the aging eye redox regulation and therapeutic treatment of cataract disease; synergism of natural antioxidant imidazole-containing amino acid-based compounds, chaperone, and glutathione boosting agents: a systemic perspective on aging and longevity emerged from studies in humans. 2046 77

Reactive oxygen species (ROS) generated in the presence of O(2) by mitochondria, phagocytic cells, peroxisomes, and cytochrome P450 enzymes under physiological conditions, may play a dual function in the human organism. On the one hand, they participate in cell signal transduction cascades, leading to the activation of some transcription factors responsible for regulating of the expression of genes relevant for cell growth and differentiation. On the other hand, they cause oxidative damage of cellular DNA, protein and lipids, resulting in the initiation or development of numerous diseases such as cancer, cardiovascular diseases, type 2 diabetes mellitus, cataract, rheumatoid arthritis, or different neurodegenerative diseases. Both endogenous compounds (glutathione, ubiquinol, urate, bilirubin) and enzymes (superoxide dismutase, catalase, glutathione peroxidase) are engaged in the detoxification of ROS. In addition, numerous dietary components such as vitamin C, vitamin E, carotenoids, and polyphenols are thought to be involved in the antioxidant defense system. The present review article is focused on the summary and the assessment of research on the impact of dietary antioxidants in the prevention of chronic diseases, particularly cancer and cardiovascular diseases.
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PMID:A review of natural and synthetic antioxidants important for health and longevity. 2066 18


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