Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats

P. F. Kador, E. F. Secchi, M. J. Lizak, L. Rodriguez, K. Blessing, S. Sato

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1 Scopus citations

Abstract

Purpose. Several recent studies with the sorbitol dehydrogenase (SDH) inhibitors S-88-0773 (4-[4-(N,N-dimethylsulfamoyl)-piperazino]-2-methyl- pyrimidine) and its active metabolite 4-[4-(N,N-dimethyl-sulfamoyl)-piperazino]-2-hydroxymethyl-pyrimidine (CP-166,572) suggest that inhibition of SDH may be beneficial in delaying the onset of diabetic complications due to their ability to ameliorate redox changes associated with polyol metabolism. To demonstrate the relative importance of SDH versus aldose reductase inhibition on sugar cataract formation, cataract formation was monitored in 50% galactose-fed and diabetic rats treated with/without the SDH inhibitors S-88-0773 or CP-166,572 or the aldose reductase inhibitors (ARIs) AL-1576 or Ponalrestat. Methods. Diabetes was induced in young 50 g rats with streptozotocin while galactosemia was produced by feeding diet containing 50% galactose. Inhibitors were administered in the diet, 0.06% for the SDH Inhibitors and Ponalrestat, 0.0125% for AL-1576. Cataract formation was monitored by hand-held slit lamp. Polyol levels were measured by GLC in one lens while flux studies were conducted by 19F-NMR in the contralateral lens through in vitro incubation in TC-199 media containing 3-fluoro-3-deoxyglucose (3-FDG). Results. Sugar cataract formation was accelerated in diabetic rats treated with SDH inhibitors while no difference in cataract formation was observed in galactose-fed rats treated with/without SDH inhibitors. Cataract formation was inhibited in both diabetic and galactosemic rats by either Ponalrestat or AL-1576. Conclusions. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalyzed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.

Original languageEnglish (US)
Pages (from-to)S190
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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