ALDOSE REDUCTASE INHIBITORS AND GALACTOSE TOXICITY IN NEONATAL AND MATERNAL RAT LENSES

We reported that n utero galactose-induced cataracts could be inhibite d if aldose reductase inhibitors (ARIs) were included in the galactose diet of pregnant rats. These studies involved morphological and cytoc hemical approaches. We undertook this investigation to evaluate the ef fects of ARIs in preventing the formation, accumulation and depletion of dulcitol in lenses of in utero galactose exposed neonates and in mo thers during and following pregnancy. Sprague Dawley rats were fed Pur ina Rat Chow with 50% galactose either with or without 15mg Sorbinil o r 1mg Eisai compound E-0722/day/Kg body weight during and following pr egnancy. The lenses of neonates and mothers were processed to determin e dulcitol concentrations. At parturition there was a significant amou nt of dulcitol in the lenses of pups and their mothers, which reduced rapidly in the lenses of pups regardless of the diet fed to the nursin g mother. While galactose had a cross-placental but not a milk-mediate d effect, the ARIs had both cross-placental and milk-mediated effects on dulcitol accumulation and depletion, respectively. The galactose fe eding of mothers post-parturition maintained the high lenticular dulci tol concentration and the absence of galactose led to a reduction in l enticular dulcitol. The correlation between dulcitol accumulation and cataract development is discussed.