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 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