Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of vitamin E-containing liposome on experimental sugar cataract formation in vitro was investigated. The lenses of male Wistar rats aged 6 weeks were prepared by incubating with 55. 6 mM glucose with vitamin E-containing liposome (dipalmitoyl phosphatidylcholine: DPPC). We examined the formation of lens opacity and assayed vitamin E and its related compounds. Incubation with vitamin E-containing liposome prevented sugar cataract formation. In Addition, vitamin E concentration in lens was significantly elevated by incubation with vitamin E-containing liposome. In lenses of the high level glucose group incubated without vitamin E-containing liposome, lipid peroxide (LPO) content was increased, but in lenses of the high-level glucose group incubated with vitamin E-containing liposome the increase was significantly inhibited at each incubation time. Vitamin E had no effect either on the decrease of reduced glutathione (GSH) or the increase of sorbitol content in lens incubated with high level glucose medium. In conclusion vitamin E-containing liposome was transported from medium to lens well and was significantly effective in preventing experimental sugar cataract formation in vitro. The protective effects of vitamin E are probably caused not only by its antioxidative action.
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PMID:[Effect of vitamin E-containing liposome on experimental sugar cataract]. 275 Jun 6

In this study, we compared the thiol/disulfide status and the protein profiles for a group of normal lenses (over 60 years old) and a group of age matched cataractous lenses. In agreement with previous reports we found that the severity of the lens opacity and the color of the nucleus correlated well with the decrease of soluble proteins and increase of guanidine insoluble proteins. However, the decrease of nonprotein thiols and protein thiols was associated only with the pigmentation of the lenses. We discovered that protein-thiol mixed disulfide profiles provided new information on the lens biochemical changes. In the normal lens, we found nearly 10% of the total nonprotein thiols bound to the protein. There were two species of protein-thiol mixed disulfides, protein-GSH and protein-cysteine with the former 3-4 times higher than the latter. In the cataractous lens the mean value of some species was elevated two-fold whereas in the noncataractous pigmented lens both protein-thiol mixed disulfides were elevated but the protein-cysteine species showed more drastic increase (three-fold in one case and 13-fold in another case). It is therefore concluded that the formation of protein-thiol mixed disulfides may play a more critical role in cataractogenesis than does protein-protein disulfide formation.
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PMID:Effect of opacification and pigmentation on human lens protein thiol/disulfide and solubility. 279 32

The relationship between the activity of the antioxidant defense enzyme glutathione peroxidase (GSH-PX) and the degree of cataract (lens opacity) was examined in 14 Emory mice at the age of 2, 7 and 10 months. Significant decreases in specific GSH-PX activity (mU/mg wet tissue) in the lens as well as in the residual eye tissue were found between 2 and 10 months of age, showing a highly significant correlation of this decrease (r = 0.590, p approximately 0.001) with the increasing degree of turbidity of the lenses. The results are discussed with regard to the changes of antioxidant mechanisms during cataractogenesis and aging. The role of the maintenance of an optimal level of GSH-PX and other well-known antioxidants (enzymes, vitamins, trace elements including iodide) for a delay of cataractogenesis is pointed out.
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PMID:[Changes of Glutathione Peroxidase Activity in Eye Tissues of Emory Mice in Relation to Cataract Status and Age]. 814 88

Oxidative stress has long been speculated to play an important role in cataractogenesis. In the H2O2-induced cataract model, rat lens showed extensive biochemical damage but very mild morphological changes after being exposed to H2O2 (0.5 mM) for 24 hr in culture. This damage included reduced glutathione (GSH) depletion, protein-GSH mixed disulfide (PSSG) elevation but not protein-protein disulfide (PSSP) formation. In order to understand the role of protein-thiol mixed disulfide formation in relation to the sequence of events during cataract induction, we conducted a long term H2O2 exposure study for up to 96 hr to monitor the dynamic changes in GSH and PSSG levels, the formation of PSSP aggregate, protein solubility, and the progression in lens opacity. Rat lenses were cultured in 0.5 mM H2O2 and harvested at intervals of 24, 48, 72 and 96 hr for the examination of morphological and biochemical changes. Contralateral lenses cultured in H2O2-free media were used as controls. It was found that the lenses had only patchy opacity at the equator after 24 hr, but became hydrated suddenly at 48 hr (31% heavier than the control), with an opacity which involved the entire outer cortical region. By 72 hr incubation, the nucleus was opacified. Lens GSH progressively decreased with time of H2O2 exposure, 40% was lost by 24 hr and over 95% by 48 hr. There was a concomitant elevation of PSSG, 16-fold over the controls by 24 hr and 45-fold by 48 hr followed by a decline to 34-fold after 72 hr. In addition, the level of protein-cysteine mixed disulfide (PSSC) was elevated after 48 hr incubation in H2O2. At this time point, PSSP aggregates began to appear both in water soluble (WS) and urea soluble (US) fractions along with a drastic reduction in protein solubility. Western blot analysis of the protein fractions identified beta and gamma, but not alpha-crystallin in the disulfide-containing aggregates. The lens clarity and biochemical changes partially recovered if the oxidant was removed within 24 hr, indicating a potential therapeutic role for antioxidants. The complete normalization of PSSG level under this recovery condition signifies that cells may have a natural defense system for controlling PSSG elevation.
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PMID:The effect and recovery of long-term H2O2 exposure on lens morphology and biochemistry. 840 82

The effect of glutathione (GSH) isopropyl ester on the progression of X-ray-induced cataract was investigated in rats. Intraperitoneal administration of 20 mg/kg GSH isopropyl ester, three times weekly, 1 day after a single irradiation dose delayed the progression of X-ray-induced cataracts significantly. The amount of non-protein SH groups and the Na+/K+ ratio in the lenses of drug-treated rats were maintained at the normal levels even 27 weeks after irradiation. Posttreatment with the drug resulted in a significantly lower level of malondialdehyde in the irradiated lenses than in the nontreated lenses. When 500 mg/kg GSH-isopropyl ester was administered by i.p. injection to normal rats, the GSH-ester was detected in plasma and aqueous humor after 15 min. In the lenses of the GSH-isopropyl ester-injected rats, the GSH level was 120% of that in the non-treated rats after 4 h, suggesting that GSH-isopropyl ester is transported from the aqueous humor to the lens and there converted to GSH after about 4 h. Our observations lead us to conclude that the delay of X-ray-induced lens opacity progression is due to maintenance of normal lenticular GSH levels achieved by post-irradiation administration of GSH-isopropyl ester. However, continuous administration of 100 mg/kg after irradiation had no effect on the progression of cataracts induced by X-rays.
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PMID:Glutathione isopropyl ester (YM737) inhibits the progression of X-ray-induced cataract in rats. 844 22

The determination of S-(1,2-dicarboxyethyl)glutathione and reduced glutathione (GSH) in the rabbit lens and liver was developed using an isotachophoretic analyser. The recovery of S-(1, 2-dicarboxyethyl)GSH from the rabbit liver after ion-exchange treatment was 96.8 +/- 11.3% (n=3). The contents of S-(1,2-dicarboxyethyl)GSH in the rabbit lens and liver were 219.9 +/- 29.1 (n=5) and 44.0 +/- 13.5 (n = 8) nmol/g, respectively. The contents of S-(1, 2-dicarboxyethyl)GSH in the lens and GSH in the lens and liver of naphthalene-treated rabbits was also determined by this method 24 hours after naphthalene administration, at which time the axial opacity "spichen" was observed at the equatorial region of the lens. The content of S-(1,2-dicarboxyethyl)GSH in the lens decreased in proportion to the content of GSH. During the further development of true lens opacity after naphthalene administration, the S-(l, 2-dicarboxyethyl)GSH content further compared with that in the spichen stage, but the S-(1, 2-dicarboxyethyl)GSH content of the lens that did not develop true opacity after naphthalene administration returned to the normal level. The change of S-(1, 2-dicarboxyethyl)GSH content of the lens in the spichen and true opacity stages coincided with that of GSH content. On the other hand, the content of GSH of the liver decreased markedly until 24 hours after naphthalene administration, then returned to normal, irrespective of whether true opacity did or did not subsequently develop.
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PMID:S-(1,2- dicarboxyethyl)glutathione and glutathione in lens and liver of napthalene-treated rabbits. 883 38

It has been previously shown in H2O2-induced cataract model in the rat lens that protein-GSH (PSSG) formation precedes protein-protein disulfide (PSSP) conjugation and lens opacity. This elevated PSSG spontaneously reduces to a normal level when H2O2 is removed. To verify if thioltransferase (TTase), an enzyme that is known in other tissues to dethiolate PSSG, takes part in this recovery process, we examined the relationship of PSSG and TTase in this cataract model. To ensure enough tissue would be available for various biochemical studies, H2O2 induced cataract in pig lens was established and validated with the rat lens model. The study was divided into two parts. One part was to examine the effect of H2O2 concentration, ranging from 0.1 mM-10 mM, during 24 hr. Another part was to study the H2O2 (1.5 mM) induced cataract progression and recovery, parallel to the long-term study in rat lenses reported previously. These lenses were compared for transparency, wet weight, GSH, PSSG levels and the activity of two redox regulating enzymes, glutathione reductase (GR) and TTase. For the most part, pig lens responded to oxidation parallel to the rat lens except that a higher concentration of H2O2 was needed to achieve the same results. Damage induced by H2O3 was concentration dependent. In general TTase activity and GSH level were depleted with a concomitant increase in PSSG. The D50 (50% damage) for GSH in pig lens was 1.5 mM H2O2 (0.5 mM for rat lens) which was chosen for further studies in cataract progression and recovery. At 1.5 mM H2O2, pig lens showed superficial opacity within 24 hr and deeper cortical opacity in 48 hr. The pre-exposed lens became less cloudy when H2O3 was removed from the medium. Incubation of the lens in 1.5 mM H2O2 for one day also induced 50% GSH depletion and four fold PSSG elevations. This accumulated PSSG was dethiolated spontaneously in the absence of H2O2, similar to the findings in the rat lens and human lens models. In contrast protein-cysteine (PSSC) showed little change and did not respond to the recovery condition. TTase lost 50% activity in these lenses during 24-hr H2O3 exposure but regained most of it under recovery. The study on rat lens showed similar results as before, therefore only data on the relationship of TTase activity to PSSG level during cataract development and recovery is reported here. It was found that in the H2O2 (0.5 mM)-exposed rat lenses, the TTase activity was depleted but PSSG accumulation was accelerated within 8 hr. Both recovered quickly (within 8 hr) as soon as the oxidant was removed. Therefore, protein thiolation and dethiolation processes in the cultured rat or pig lenses display a mirror image with the activity pattern of TTase. Based on the close relationship between lens TTase and PSSG indicated above, it is speculated that TTase may regulate PSSG and maintain it at a low concentration in situ. This repair process may contribute to the improved transparency during recovery. Further studies are planned to substantiate this hypothesis.
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PMID:Relationship of protein-glutathione mixed disulfide and thioltransferase in H2O2-induced cataract in cultured pig lens. 924 98

In a random trial 50 patients with unilateral/ bilateral idiopathic immature senile cataract (cortical n = 25, nuclear n = 25) requiring surgery at least in one eye were included in the present study. Reduced glutathione (GSH), vitamin E, malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were studied in these patients receiving either vitamin E (n = 12 in each subgroup) or placebo (n = 13 in each group) for 30 days. A comparable increase of vitamin E in both types of lens homogenates of cataractous patients was observed in the study group. The level of GSH in cortical cataractous lenses in the study group was significantly raised (p < 0.001) whereas it was not increased significantly in nuclear cataractous lenses (p > 0.05) as compared to the placebo group. The percentage decrease in MDA levels was greater in cortical cataracts (38.07%) than in the nuclear type (27.94%). The activity of GSH-Px in cortical lenses was higher than that in the nuclear cataractous lens. The change in the size of lens opacity in cortical cataractous patients receiving vitamin E therapy was significantly decreased as compared to the placebo group. There may be a direct modulating effect of vitamin E on some GSH-related enzymes and the cortex of the lens might be protected more than the nucleus.
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PMID:Protective function of alpha-tocopherol against the process of cataractogenesis in humans. 1074 28

Vanadium compounds are potent in controlling elevated blood glucose levels in experimentally induced diabetes. However the toxicity associated with vanadium limits its role as therapeutic agent for diabetic treatment. A vanadium compound sodium orthovanadate (SOV) was given to alloxan-induced diabetic Wistar rats in lower doses in combination with Trigonella foenum graecum, a well-known hypoglycemic agent used in traditional Indian medicines. The effect of this combination was studied on lens morphology and glucose metabolism in diabetic rats. Lens, an insulin-independent tissue, was found severely affected in diabetes showing visual signs of cataract. Alterations in the activities of glucose metabolizing enzymes (hexokinase, aldose reductase, sorbitol dehydrogenase, glucose-6-phosphate dehydrogenase) and antioxidant enzymes (glutathione peroxidase, glutathione reductase) besides the levels of related metabolites, [sorbitol, fructose, glucose, thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH)] were observed in the lenses from diabetic rats and diabetic rats treated with insulin (2 IU/day), SOV (0.6 mg/ml), T. f. graecum seed powder (TSP, 5%) and TSP (5%) in combination with lowered dose of vanadium SOV (0.2 mg/ml), for a period of 3 weeks. The activity of the enzymes, hexokinase, aldose reductase and sorbitol dehydrogenase was significantly increased whereas the activity of glucose-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase decreased significantly in lenses from 3 week diabetic rats. Significant increase in accumulation of metabolites, sorbitol, fructose, glucose was found in diabetic lenses. TBARS measure of peroxidation increased whereas the levels of antioxidant GSH decreased significantly in diabetic condition. Insulin restored the levels of altered enzyme activities and metabolites almost to control levels. Sodium orthovanadate (0.6 mg/ml) and Trigonella administered separately to diabetic animals could partially reverse the diabetic changes, metabolic and morphological, while vanadate in lowered dose in combination with Trigonella was found to be the most effective in restoring the altered lens metabolism and morphological appearance in diabetes. It may be concluded that vanadate at lowered doses administered in combination with Trigonella was the most effective in controlling the altered glucose metabolism and antioxidant status in diabetic lenses, these being significant factors involved in the development of diabetic complications, that reflects in the reduced lens opacity.
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PMID:Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rat lenses. 1588 58

L-Tryptophan (Trp) is an essential amino acid and its deficiency is involved in various pathologies. In this present investigation an attempt was made to study the role of tryptophan and its metabolites in cataract formation in wistar rats. Rats were divided and maintained in 3 groups, Group A--control; Group B--marginal-tryptophan and Group C--Tryptophan-deficient diet for 3 months. Slit lamp microscope observations indicated lenticular opacities in Group-C (tryptophan-deficient) rats. In the rats that were maintained on tryptophan deficient diet, a decrease in protein content, kynurenines, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-tranferase (GSTs) and tryptophan-fluorescence intensities and an increase in lipid peroxidation indicative of oxidative stress have been observed. The above changes were normalized in the rats on supplementation of 0.05% tryptophan (Group-B) in their diets. These results suggest that tryptophan-deficiency in the diet leads to an overall significant decrease in kynurenines and levels of antioxidant enzymes (except SOD) in ocular tissue with a concomitant lenticular opacification. The results suggest that diet with adequate tryptophan has protective influence and is of immense benefit in mitigating the changes that may otherwise contribute to the lenticular opacities.
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PMID:Influence of kynurenines in pathogenesis of cataract formation in tryptophan-deficient regimen in Wistar rats. 1758 90


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