Aldose reductase inhibitors and prevention of galactose cataracts in rats.
Our previous studies have shown that the aldose reductase inhibitor (ARI), sorbinil, prevents galactose-induced alterations and cataracts in rat lenses. We have now used sorbinil as well as another ARI, Eisai compound E-0722, to determine their potency in inhibiting aldose reductase- and galactose-induced alterations in lens morphology and Na+-K+-ATPase activity. Young Sprague Dawley rats were fed Purina Rat Chow plus 50% galactose, with or without 15 mg sorbinil, 0.15, 0.5 or 1.0 mg of E-0722/kg body weight per day. Controls were given Purina Rat Chow with or without ARIs. Lenses were studied for up to 60 days following the initiation of the diet using morphological, cytochemical and biochemical approaches to assess any alterations in the lens. While galactose-induced damage and cataracts were delayed by low doses (0.15 mg and 0.5 mg) of E-0722, they were completely prevented by the administration of 15 mg of sorbinil or 1 mg of E-0722/kg body weight per day. This study further showed that just 1 mg of E-0722 was more effective in preventing cataracts than 15 mg sorbinil. Thus it appeared that E-0722 was a more potent inhibitor of aldose reductase than sorbinil.
Unakar
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N
Department of Biological Sciences, Oakland University, Rochester, Michigan 48309-4401.
Tsui
J
J
Johnson
M
M
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005690:Galactose / Q000009:adverse effects*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D013997:Time Factors
D007093:Imidazoles; D048289:Imidazolidines; C037070:M 79175; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase; C026411:sorbinil; D005690:Galactose