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)

Naphthalene-induced rat cataract is a useful experimental cataract--however, because of its short survival period, studies using this model have been for limited purposes. Based on the consideration that the short survival might be caused by systemic toxicity of an overdose of naphthalene administration (1 g/kg body weight every other day), the authors successfully established a naphthalene-induced cataract with mild progression in Brown-Norway rats. The naphthalene administration proposed is to initially administer 0.5 g/kg and after a 1-week interval 1 g/kg of 10% naphthalene once or twice a week through a stomach tube. While the type of lens opacification induced in the two groups administered once and twice a week, respectively, was the same as that seen by the previous administration method, the progression of lens opacification seen in the groups showed a dose-dependent increase. The survival rate in the rats given naphthalene every other day according to the old method was 50% at the 6th week and 0% at the 9th week. Survival of the two new groups was 70 and 60% at the 30th week, respectively. This new type of naphthalene-induced rat cataract should be a suitable model for long-term observations.
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PMID:A mild progression type of naphthalene-induced cataract in brown-Norway rats. 857 60

Naphthalene-induced cataract in rat lenses can be completely prevented by AL01576, an aldose reductase inhibitor (ARI). In an attempt to understand the mechanism of this inhibition, several ARIs were examined to compare their efficacies in preventing naphthalene cataract, using both in vitro and in vivo models. Two classes of ARIs were tested: One group including AL01576, AL04114 (a AL01576 analog) and Sorbinil contained the spirohydantoin group, while Tolrestat contained a carboxylic acid group. Furthermore, to clarify if aldose reductase played a role in naphthalene-induced cataractogenesis in addition to its role in sugar cataract formation, a new dual cataract model was established for ARI evaluations. This was achieved by feeding rats simultaneously with high galactose and naphthalene or incubating rat lenses in culture media containing high galactose and naphthalene dihydrodiol. Under these conditions, both cortical cataract and perinuclear cataract developed in the same lens. It was found that at the same dosage of 10 mg/kg/day, both AL01576 and AL04114 completely prevented all morphological and biochemical changes in the lenses of naphthalene-fed rats. Sorbinil was less efficacious, while Tolrestat was inactive. AL01576 showed a dose-response effect in preventing naphthalene cataract and at 10 mg/kg/day, it was also effective as an intervention agent after cataractogenesis had begun. With the dual cataract model, Tolrestat prevented the high galactose-induced cortical cataract but showed no protection against the naphthalene-induced perinuclear cataract. AL01576, on the other hand, prevented both cataract formations. Results for dulcitol and glutathione levels were in good agreement with the morphological findings. AL04114, and ARI as potent as AL01576 but without its property for cytochrome P-450 inhibition, displayed similar efficacy in preventing naphthalene cataract. Based on these results, it was concluded that the prevention of the naphthalene cataract probably results from inhibition of the conversion of naphthalene dihydrodiol to 1,2-dihydroxynaphthalene and that the effect of the ARIs cannot be explained by their inhibition of the dihydrodiol dehydrogenase activity of aldose reductase.
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PMID:Inhibition of naphthalene cataract in rats by aldose reductase inhibitors. 867 Jul 42

Rapid-onset cataracts were induced in SPF C57 bl/6 mice by intraperitoneal administration of naphthalene following cytochrome P-450 isozyme induction with phenobarbital. Several L-cysteine prodrugs with masked sulfhydryl groups in the form of thiazolidine-4-carboxylic acids, as well as N-acetyl-L-cysteine, N,S-bis-acetyl-L-cysteine and glutathione ethyl ester, were evaluated for their ability to maintain hepatic and lenticular glutathione at near-normal levels and to prevent naphthalene-induced cataract formation. Each prodrug was administered at three specified times to a cumulative total of 1.5 mole equivalents of the single dose of naphthalene. Three L-cysteine prodrugs delayed but did not prevent cataract formation in 40-60% of the mice over a 72-hr period, while eight of the 13 compounds produced cataract yields similar to the naphthalene control animals, i.e. 83% in 72 hr. However, two L-cysteine prodrugs, 2(R,S)-methylthiazolidine-4(R)-carboxylic acid (MTCA) and 2(R,S)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA), prevented cataract formation in 20 of 21 and 12 of 12 mice, respectively, and maintained hepatic reduced glutathione levels at 82% and 51% of untreated controls. In contrast, glutathione was depressed to 3% of the normal value in those animals treated with naphthalene alone. Lenticular glutathione values were depressed, albeit minimally, in all naphthalene-treated mice regardless of administration of either MTCA or PTCA. The mice protected with either MTCA or PTCA showed no visible effects of naphthalene toxicity or lens opacities at any time. It can be concluded that these L-cysteine prodrugs were effective in preventing naphthalene-induced cataract and maintaining near-normal hepatic glutathione levels.
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PMID:Prevention of naphthalene-induced cataract and hepatic glutathione loss by the L-cysteine prodrugs, MTCA and PTCA. 879 61

Human and other mammalian lens proteins are composed of three major crystallins: alpha-, beta-, and gamma-crystallin. alpha-Crystallin plays a prominent role in the supramolecular assembly required to maintain lens transparency. With age, the crystallins, especially alpha-crystallin, undergo posttranslational modifications that may disrupt the supramolecular assembly, and the lens becomes susceptible to other stresses resulting in cataract formation. Because these modifications occur even at a relatively young age, it is difficult to obtain pure, unmodified crystallins for in vitro experiments. alpha-Crystallin is composed of two subunits, alphaA and alphaB. Before the application of recombinant DNA technology, these two alpha-crystallin subunits were separated from calf lens in the denatured state and reconstituted by the removal of the denaturant, but they were not refolded properly. In the present studies, we applied the recombinant DNA technology to prepare native, unmodified alphaA- and alphaB-crystallins for conformational and functional studies. The expressed proteins from Escherichia coli are in the native state and can be studied directly. First, alphaA and alphaB cDNAs were isolated from a human lens epithelial cell cDNA library. The cDNAs were cloned into a pAED4 expression vector and then expressed in E. coli strain BL21(DE3). Pure recombinant alphaA- and alphaB-crystallins were obtained after purification by gel filtration and DEAE liquid chromatography. They were subjected to conformational studies involving various spectroscopic measurements and an assessment of chaperone-like activity. alphaA- and alphaB-crystallins have not only different secondary structure, but also tertiary structure. 1-Anilino-8-naphthalene sulfonate fluorescence indicates that alphaB-crystallin is more hydrophobic than alphaA-crystallin. The chaperone-like activity, as measured by the ability to protect insulin aggregation, is about 4 times greater for alphaB- than for alphaA-crystallin. The resulting data provide a base line for further studies of human lens alpha-crystallin.
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PMID:Conformational and functional differences between recombinant human lens alphaA- and alphaB-crystallin. 904 37

alpha-Crystallin, a major protein of the eye lens, is known to have chaperone activity in preventing heat-induced aggregation of enzymes and other crystallins. In this study, we investigate the ability of alpha-crystallin to inhibit UV-light-induced aggregation of other lens proteins and the effect of exposure of alpha-crystallin to UV irradiation on its chaperone activity. The chaperone activities of alpha-crystallin preincubated at different temperatures were found to be different and could be correlated with its change in quaternary structure as determined by the fluorescence probe ANS (8-anilo-1-naphthalene sulfonate). alpha-Crystallin can inhibit the aggregation of gamma-crystallin from UV irradiation at room temperature, and the preheated alpha-crystallins provide more protection than the native one. Upon irradiation by UV light, alpha-crystallin gradually lost its ability to protect beta-crystallin against thermal aggregation. The loss of the chaperone efficacy of alpha-crystallin to protect other lens proteins may shed light on human cataract formation induced by long-term exposure to UV irradiation.
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PMID:alpha-Crystallin acting as a molecular chaperonin against photodamage by UV irradiation. 918 67

The effects of aldose reductase inhibitors on lens protein modifications induced by naphthalene-1,2-dihydrodiol were investigated in vitro to confirm the role of aldose reductase on naphthalene cataract formation. HPLC analysis of naphthalene-1, 2-dihydrodiol incubated with aldose reductase and NAD+indicated the formation of a metabolite peak corresponding to 1,2-naphthoquinone. Soluble proteins from rat lenses prepared by gel filtration of crude lens extracts through Sephadex PD-10, incubated with naphthalene-1, 2-dihydrodiol in the presence of NAD+displayed an absorbance ca 450 nm and their spectra were essentially identical to those of 1, 2-naphthoquinone-protein adducts. Similar spectra were also obtained from proteins isolated from the intact rat lens after in vitro incubation in medium containing naphthalene-1,2-dihydrodiol. The spectra obtained from lens proteins incubated with 1, 2-dihydroxynaphthalene were distinct from those of either naphthalene-1,2-dihydrodiol or 1,2-naphthoquinone. Aldose reductase inhibitors possessing either hydantoin or carboxylic acid groups prevented protein modification induced by naphthalene-1, 2-dihydrodiol but not protein modification induced by 1, 2-dihydroxynaphthalene or 1,2-naphthoquinone. Therefore, the metabolite formed from naphthalene-1,2-dihydrodiol by aldose reductase is 1,2-naphthoquinone. Lens proteins modified by naphthalene-1,2-dihydrodiol appear essentially identical to protein adducts formed with 1,2-naphthoquinone and their formation can be prevented by both hydantoin and carboxylic acid containing aldose reductase inhibitors.
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PMID:Prevention of naphthalene-1,2-dihydrodiol-induced lens protein modifications by structurally diverse aldose reductase inhibitors. 1032 74

The effect of vitamin E acetate (VEA) eye drops on naphthalene-induced cataract in rats was investigated by Scheimpflug image analysis. The control group was administered only naphthalene (1 g/kg), while the other group was additionally given 1% VEA eye drops into both eyes 5 times a day every day for 9 weeks from the start of naphthalene treatment. During those 9 weeks, the changes of the crystalline lens were documented by an anterior eye segment analysis system (EAS-1000, NIDEK) once a week in mydriasis (Mydrin-P, Santen Pharmaceutical Co., Ltd.). The characteristic density values of the anterior deeper cortex regions were measured. The light scattering intensity of lenses from VEA eye drop-treated animals was significantly lower than that of animals without VEA treatment. This difference was found 1 week, 4 weeks, and from 7 to 9 weeks after the start of naphthalene application. VEA eye drops may have the potential to delay the progression of naphthalene-induced cataract in rats.
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PMID:Effect of vitamin E eye drops on naphthalene-induced cataract in rats. 1046 73

Administration of naphthalene is known to cause cataract formation in rats and rabbits and naphthalene-initiated cataract is frequently used as a model for studies on senile cataract in humans. Oxidative stress has been implicated in the mechanism of naphthalene-induced cataract. Curcumin, a constituent of turmeric, a spice used in Indian curry dishes, is an effective antioxidant and is known to induce the enzymes of glutathione-linked detoxification pathways in rats. During the present studies, we have examined whether low levels of dietary curcumin could prevent naphthalene-induced opacification of rat lens. The presence of apoptotic cells in lens epithelial cells was also examined by catalytically incorporating labeled nucleotide to DNA with either Klenow fragment of DNA polymerase or by terminal deoxynucleotidyl transferase (TdT), which forms polymeric tail using the principle of TUNEL assay. The results of these studies demonstrated that the rats treated with naphthalene and kept on a diet supplemented with only 0.005% (w/w) curcumin had significantly less opacification of lenses as compared to that observed in rats treated only with naphthalene. Our studies also demonstrate, for the first time, that naphthalene-initiated cataract in lens is accompanied and perhaps preceded by apoptosis of lens epithelial cells and that curcumin attenuates this apoptotic effect of naphthalene.
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PMID:Dietary curcumin prevents ocular toxicity of naphthalene in rats. 1081 89

N-acetyl-p-benzoquinone imine (NAPQI), a semiquinone metabolite of acetaminophen, produces cataract in mice. Naphthalene is biotransformed to the cataractogenic metabolite 1,2-naphthoquinone (NQ). Intracameral injection of NAPQI elicits a rapid increase in free intracellular Ca2+ in the lens epithelium and calpain activation before lens opacification begins. In order to test whether the cellular response is a common feature of quinone-induced cataracts, we injected in this work 1,2-naphthoquinone (NA) in the anterior chamber of mouse eye and followed cellular responses in the lens prior to opacity development. A marked rise in free intracellular Ca2+ in the lens epithelium and concurrent activation of calpain were observed within 1 hr after NQ injection preceding lens opacity development. These results support the suggestion that Ca2+ release and calpain activation are involved in the mechanism of quinone-induced cataractogenesis.
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PMID:Naphthoquinone-Induced cataract in mice: possible involvement of Ca2+ release and calpain activation. 1157 69

Anticataract activity of Ambroxol, Spirulina and Vitamin E was examined using the naphthalene cataract model. Adult female albino rats of Wistar strain weighing between 180 and 220 grams were taken and divided into eight groups. Group I received light liquid paraffin 5 ml/kg/ day p.o. for 6 weeks. Group II received naphthalene solution 0.5 gm/kg/ day p.o. for first three days and 1 gm/kg/day p.o. thereafter for six weeks. Group III received Ambroxol suspension in 0.5% carboxy methyl cellulose (CMC) at the dose of 100 mg/kg/day p.o. alongwith naphthalene. Group IV received Spirulina in distilled water at the dose of 1500 mg/kg/ day p.o. alongwith naphthalene. Group V received Vitamin E emulsion at the dose of 50 mg/kg/day p.o. alongwith naphthalene. Group VI received Ambroxol alone at the dose of 100 mg/kg/day p.o. Group VII received Spirulina alone at the dose of 1500 mg/kg/day p.o. Group VIII received vitamin E alone at the dose of 50 mg/kg/day p.o. Lens glutathione, soluble protein and water content profiles revealed the preventive role of Ambroxol, Spirulina and Vitamin E in naphthalene-induced cataract in female rats.
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PMID:Effect of ambroxol, spirulina and vitamin-E in naphthalene induced cataract in female rats. 1588 59


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