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 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

In this paper various changes in glutathione level, which were influenced by balance of its synthesis, degradation, transport and utilization, were analysed in chick embryos administered with glucocorticoid (GC) or buthionine sulfoximine (BSO; an inhibitor of glutathione synthesis). When BSO (30 mumol egg-1) was administered twice to chick embryos on day 14 and 15, the GSH in both the lens and the liver decreased to 15-20% and 30-40% of the age-matched control level, respectively, between 24 and 48 hr after the second treatment, then began to recover. Although this decline in the GSH level in these tissues was greater and more prolonged in embryos treated with BSO than with GC, the former embryos maintained lens transparency even up to 144 hr by a visual examination. However, histological changes in the lens occurred after 96 hr and more significantly 144 hr after second administration of BSO. The changes mainly consisted of pale epithelial cells on the anterior peripheral surface of the lens, irregular height of the epithelial cells at the equator, clefts between the epithelium and the cortex and swelling of almost all the cortical fibers. These observations may suggest that BSO treatment could produce the beginning of a cataract. Embryos with GC-cataract revealed the following changes at 48 hr: loss of transparency, elevation of LPO (TBA-reacting substance) in the lens, the blood and the liver. These were not observed in BSO-treated embryos during the experimental period. The GC-cataract may well depend on the generation of LPO. BSO cataract, having a distinct mechanism compared to that caused by GC, develops more slowly in GSH-depleted lenses. The BSO-treated chick embryos will be a useful model to screen the risk factors which accelerate cataract formation.
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PMID:Comparison of lens biochemistry and structure between BSO-treated and glucocorticoid-treated developing chick embryos. 906 74

Mouse lens cultures were employed to study the progression of cataracts initiated by injection of buthionine sulfoximine, an inhibitor of glutathione (GSH) biosynthesis. Culture of lenses removed from untreated mice on postnatal day 7, for 48 hr in the presence of 4 mm BSO, resulted in only limited cataractous changes. To enable substantial progression of cataracts in vitro, it was therefore necessary to pretreat the mice with BSO prior to lens culture. A single injection of BSO (4 nmol mg-1 lens), administered on day 7, resulted in >90% depletion of lens GSH within 3 days, but no visible cataractous changes. The clear lenses were incubated for 29+/-1 hr at 37 degrees C in Medium HL-1, supplemented with EGF, insulin and Ca2+, in the presence or absence of BSO, and were scored for cataract development by previously described criteria. In the absence of BSO, only 4 of 10 lenses developed large opacities. However, in the presence of 4 mm BSO, 40 out of 45 experimental lenses developed opacities affecting at least 50% of the lens visual field and were scored as stages 1C-4, depending upon the extent and density of the cataracts. In addition, three lenses had opacities involving 20-50% of the field (stage 1B). By contrast, less than 10% of lenses from untreated mice incubated in the absence of BSO developed opacities. The cataracts developed in 4 mm BSO were accompanied by reduction of lens glutathione levels to <0.010 nmol mg-1 lens. They were almost completely prevented by 1 mm ascorbate, 2 mm GSH, 2 mm GSH monoethyl ester and 2 mm cysteamine. GSH and GSH ester maintained lens glutathione content between 0.1 and 0.2 nmol mg-1 in the presence of BSO, whereas ascorbate did not prevent near-total GSH depletion. The prevention of cataracts by thiols and ascorbate was confirmed by lens Na/K ratios not significantly different from those in control lenses. The above combination of GSH depletion in vivo by a single injection of BSO, followed 3 days later with lens culture in the presence of BSO, may yield a useful system to elucidate and control the biochemical mechanisms involved in oxidative cataract induction by this GSH-depleting agent.
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PMID:Progression of mouse buthionine sulfoximine cataracts in vitro is inhibited by thiols or ascorbate. 929 71

The effects of N-acetylcysteine amide (NACA), a free radical scavenger, on cataract development were evaluated in Wistar rat pups. Cataract formation was induced in these animals with an intraperitoneal injection of a glutathione (GSH) synthesis inhibitor, l-buthionine-(S,R)-sulfoximine (BSO). To assess whether NACA has a significant impact on BSO-induced cataracts, the rats were divided into four groups: (1) control, (2) BSO only, (3) NACA only, and (4) NACA+BSO. The control group received only saline ip injections on postpartum day 3, the BSO-only group was given ip injections of BSO (4mmol/kg body wt), the NACA-only group received ip injections of only NACA (250mg/kg body wt), and the NACA+BSO group was given a dose of NACA 30min before administration of the BSO injection. The pups were sacrificed on postpartum day 15, after examination under a slit-lamp microscope. Their lenses were analyzed for selective oxidative stress parameters, including glutathione (reduced and oxidized), protein carbonyls, catalase, glutathione peroxidase, glutathione reductase, and malondialdehyde. The lenses of pups in both the control and the NACA-only groups were clear, whereas all pups within the BSO-only group developed well-defined cataracts. It was found that supplemental NACA injections during BSO treatment prevented cataract formation in most of the rat pups in the NACA+BSO group. Only 20% of these pups developed cataracts, and the rest retained clear lenses. Further, GSH levels were significantly decreased in the BSO-only treated group, but rats that received NACA injections during BSO treatment had these levels of GSH replenished. Our findings indicate that NACA inhibits cataract formation by limiting protein carbonylation, lipid peroxidation, and redox system components, as well as replenishing antioxidant enzymes.
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PMID:In vivo inhibition of l-buthionine-(S,R)-sulfoximine-induced cataracts by a novel antioxidant, N-acetylcysteine amide. 2117 25