Aldose reductase inhibitors and galactose toxicity in neonatal and maternal rat lenses.

Abstract

We reported that in utero galactose-induced cataracts could be inhibited if aldose reductase inhibitors (ARIs) were included in the galactose diet of pregnant rats. These studies involved morphological and cytochemical approaches. We undertook this investigation to evaluate the effects of ARIs in preventing the formation, accumulation and depletion of dulcitol in lenses of in utero galactose exposed neonates and in mothers during and following pregnancy. Sprague Dawley rats were fed Purina Rat Chow with 50% galactose either with or without 15mg Sorbinil or 1mg Eisai compound E-0722/day/Kg body weight during and following pregnancy. The lenses of neonates and mothers were processed to determine dulcitol concentrations. At parturition there was a significant amount 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 nursing mother. While galactose had a cross-placental but not a milk-mediated effect, the ARIs had both cross-placental and milk-mediated effects on dulcitol accumulation and depletion, respectively. The galactose feeding of mothers post-parturition maintained the high lenticular dulcitol concentration and the absence of galactose led to a reduction in lenticular dulcitol. The correlation between dulcitol accumulation and cataract development is discussed.