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

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

There is strong evidence to show that diabetes is associated with increased oxidative stress. However, the source of this oxidative stress remains unclear. Using transgenic mice that overexpress aldose reductase (AR) in their lenses, we found that the flux of glucose through the polyol pathway is the major cause of hyperglycemic oxidative stress in this tissue. The substantial decrease in the level of reduced glutathione (GSH) with concomitant rise in the level of lipid peroxidation product malondialdehyde (MDA) in the lens of transgenic mice, but not in the nontransgenic mice, suggests that glucose autoxidation and nonenzymatic glycation do not contribute significantly to oxidative stress in diabetic lenses. AR reduction of glucose to sorbitol probably contributes to oxidative stress by depleting its cofactor NADPH, which is also required for the regeneration of GSH. Sorbitol dehydrogenase, the second enzyme in the polyol pathway that converts sorbitol to fructose, also contributes to oxidative stress, most likely because depletion of its cofactor NAD+ leads to more glucose being channeled through the polyol pathway. Despite a more than 100% increase of MDA, oxidative stress plays only a minor role in the development of cataract in this acute diabetic cataract model. However, chronic oxidative stress generated by the polyol pathway is likely to be an important contributing factor in the slow-developing diabetic cataract as well as in the development of other diabetic complications.--Lee, A. Y. W., Chung, S. S. M. Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J. 13, 23-30 (1999)
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PMID:Contributions of polyol pathway to oxidative stress in diabetic cataract. 987 26

The sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases that helps regulate the lifespan of diverse organisms. The human genome encodes seven different sirtuins (SIRT1-7), which share a common catalytic core domain but possess distinct N- and C-terminal extensions. Dysfunction of some sirtuins have been associated with age-related diseases, such as cancer, type II diabetes, obesity-associated metabolic diseases, neurodegeneration, and cardiac aging, as well as the response to environmental stress. SIRT1 is one of the targets of resveratrol, a polyphenolic SIRT1 activator that has been shown to increase the lifespan and to protect various organs against aging. A number of animal studies have been conducted to examine the role of sirtuins in ocular aging. Here we review current knowledge about SIRT1 and ocular aging. The available data indicate that SIRT1 is localized in the nucleus and cytoplasm of cells forming all normal ocular structures, including the cornea, lens, iris, ciliary body, and retina. Upregulation of SIRT1 has been shown to have an important protective effect against various ocular diseases, such as cataract, retinal degeneration, optic neuritis, and uveitis, in animal models. These results suggest that SIRT1 may provide protection against diseases related to oxidative stress-induced ocular damage, including cataract, age-related macular degeneration, and optic nerve degeneration in glaucoma patients.
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PMID:The role of SIRT1 in ocular aging. 2389 78