title: In utero and milk-mediated effect of aldose reductase inhibitor on galactose cataracts.
abstract: Our previously reported investigations showed that cataracts could be induced in fetal lenses through the maternal feeding of galactose during pregnancy. We also reported that the lens opacity present at birth reverses completely by 30 days of age if there is no further post-natal exposure to galactose. This investigation was designed to investigate if an aldose reductase inhibitor (ARI) has any cross-placental effect in preventing galactose-induced cataracts in fetuses. We have also evaluated if there are any milk-mediated effects of galactose on cataract induction and of galactose and ARI on the maintenance or reversal of opacities induced in utero. Pregnant Sprague-Dawley rats were fed either 50% galactose or rat chow with or without the ARI, (2R,4S)-6-fluoro-2-methyl spirochroman-4,4'-imidazolidine-2',5'-dione (Eisai compound E-0722). Following parturition, pups of mothers from the different dietary groups were either fed by their own mothers or foster fed by lactating females fed either rat chow or 50% galactose with or without the ARI. Lenses of the pups were examined at desired intervals with light and scanning electron microscopes. We observed that: (a) both galactose and the ARI had a cross-placental effect on the fetal lenses in the development and inhibition of cataracts, respectively; (b) galactose had very little, if any, milk-mediated effect on either the induction of cataracts in newborn pups that were born with transparent lenses or the maintenance of cataracts induced in utero; (c) the ARI appeared to have a milk-mediated effect, which accelerates the reversal of cataract associated alterations in lenses of pups with cataracts induced in utero, leading to further reinstatement of lens transparency; and (d) the presence of ARI in the diet of rats during pregnancy and/or post-parturition provided continued protection to the lenses of pups that were exposed to a galactose diet following birth.
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, MI 48309.
authors.forename: N J
authors.initials: NJ
authors.lastname: Unakar
authors.forename: J Y
authors.initials: JY
authors.lastname: Tsui
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: L
authors.initials: L
authors.lastname: Dang
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005315:Fetal Diseases / Q000517:prevention & control*; D005690:Galactose; D007093:Imidazoles / Q000378:metabolism / Q000627:therapeutic use; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000648:ultrastructure; D008431:Maternal-Fetal Exchange; D008855:Microscopy, Electron, Scanning; D008895:Milk, Human / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007093:Imidazoles; D048289:Imidazolidines; C037070:M 79175; D000449:Aldehyde Reductase; D005690:Galactose