Prefeeding of aldose reductase inhibitor and galactose cataractogenesis.
Our recent investigations have shown that the Eisai compound, E-0722, (2R-4S-6-fluoro-1-2-methylspirochroman 4,4'-imidazolidine 2,5'-dione) is a more potent aldose reductase inhibitor than Sorbinil (D-6-fluorospirochroman 4,4'-imidazolidine 2,5'-dione). In the previous studies these aldose reductase inhibitors were added to the 50% galactose diet fed to rats to determine their effect on galactose-induced alterations in the lens and the development of cataract. In this report we present our results on the effect of prefeeding the aldose reductase inhibitor, E-0722, on the alterations in rat lens following subsequent feeding of galactose. For this study, young Sprague Dawley rats were prefed either rat chow or rat chow plus 50% galactose containing 1mg/day/Kg body weight of E-0722 for 1 or 2 weeks. After this dietary regimen, the animals were transferred to diets containing 50% galactose for different periods. For controls, rats were fed either rat chow or 50% galactose without the prefeeding of E-0722. Our results obtained through gross observation of the lenses, light microscopic studies of lens sections and assay of Na+-K+-ATPase (NPPase) activity show that the prefeeding of E-0722 prior to galactose feeding delays galactose-induced alterations and the development of mature cataract.
Unakar
N J
NJ
Department of Biological Sciences, Oakland University, Rochester, MI 48309-4401.
Tsui
J Y
JY
Johnson
M J
MJ
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002386:Cataract / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D004032:Diet; D005690:Galactose / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D048289:Imidazolidines; C037070:M 79175; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase; D005690:Galactose