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Science 14 December 1973:
Vol. 182. no. 4117, pp. 1146 - 1148
DOI: 10.1126/science.182.4117.1146
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Articles

Polyol Accumulation in Galactosemic and Diabetic Rats: Control by an Aldose Reductase Inhibitor

D. Dvornik 1, N. Simard-Duquesne 1, M. Krami 1, K. Sestanj 1, K. H. Gabbay 2, J. H. Kinoshita 3, S. D. Varma 3, and L. O. Merola 3

1 Department of Biochemistry, Ayerst Research Laboratories, Montreal, Quebec, Canada
2 Cell Biology, Laboratory, Endocrine Division, Children's Hospital Medical Center, Boston, Massachusetts 02115, and Department of Pediatrics, Harvard Medical School, Boston
3 Laboratory of Vision Research, National Eye Institute, Bethesda, Maryland 20015

An orally active inhibitor of aldose reductase, 1,3-dioxo-1H-benz[de]-isoquinoline-2(3H)acetic acid (AY-22,284), prevented cataractous changes in cultured lenses exposed to high concentrations of galactose. When given orally, AY-22,284 markedly decreased the accumulation of polyols in the lenses and sciatic nerves of galactosemic rats and rats with streptozotocin-induced diabetes. In addition, treatment of galactosemic rats with AY-22,284 effectively suppressed the formation of cataracts.


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