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

Peter F. Kador, Jun Inoue, E. Fillipo Secchi, Martin J. Lizak, Libaniel Rodriguez, Kazuhiko Mori, William Greentree, Karen Blessing, Petra A. Lackner, Sanai Sato

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Several recent studies with the sorbitol dehydrogenase inhibitors 4-[4- (N,N-dimethylsulfamoyl)-piperazino]-2-methylpyrimidine, SDH-1, and its active metabolite 4-[4-(N,N-dimethylsulfamoyl)-piperazino]-2- hydroxymethylpyrimidine, SDH-2, suggest that inhibition of sorbitol dehydrogenase may be beneficial in delaying the onset of diabetic complications due to their ability to ameliorate redox changes associated with polyol metabolism. To compare the relative importance of sorbitol dehydrogenase versus aldose reductase inhibition on sugar cataract formation, cataract formation was monitored in 50% galactose-fed and diabetic rats treated with/without the sorbitol dehydrogenase inhibitors SDH-1 or SDH-2 or the aldose reductase inhibitors AL 1576 or Ponalrestat. For these studies, diabetes was induced in young 50 g rats with streptozotocin while galactosemia was produced by feeding a diet containing 50% galactose. Inhibitors were administered in the diet with the diet containing 0.06% (w/w) of the sorbitol dehydrogenase inhibitors or Ponalrestat, and 0.0125% (w/w) of AL 1576. Cataract formation was monitored by hand-held slit lamp and polyol levels were measured by gas chromatography. Sugar cataract formation was accelerated in diabetic rats treated with sorbitol dehydrogenase 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. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalysed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalExperimental Eye Research
Volume67
Issue number2
DOIs
StatePublished - Aug 1998

Fingerprint

L-Iditol 2-Dehydrogenase
Galactose
Cataract
Aldehyde Reductase
S 0773
Diet
Galactosemias
Diabetes Complications
Streptozocin
Gas Chromatography
Oxidation-Reduction
Hand

Keywords

  • Aldose reductase
  • Cataract
  • Diabetes
  • Galactosemia
  • Inhibitors
  • Sorbitol dehydrogenase

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats. / Kador, Peter F.; Inoue, Jun; Secchi, E. Fillipo; Lizak, Martin J.; Rodriguez, Libaniel; Mori, Kazuhiko; Greentree, William; Blessing, Karen; Lackner, Petra A.; Sato, Sanai.

In: Experimental Eye Research, Vol. 67, No. 2, 08.1998, p. 203-208.

Research output: Contribution to journalArticle

Kador, PF, Inoue, J, Secchi, EF, Lizak, MJ, Rodriguez, L, Mori, K, Greentree, W, Blessing, K, Lackner, PA & Sato, S 1998, 'Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats', Experimental Eye Research, vol. 67, no. 2, pp. 203-208. https://doi.org/10.1006/exer.1998.0502
Kador, Peter F. ; Inoue, Jun ; Secchi, E. Fillipo ; Lizak, Martin J. ; Rodriguez, Libaniel ; Mori, Kazuhiko ; Greentree, William ; Blessing, Karen ; Lackner, Petra A. ; Sato, Sanai. / Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats. In: Experimental Eye Research. 1998 ; Vol. 67, No. 2. pp. 203-208.
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abstract = "Several recent studies with the sorbitol dehydrogenase inhibitors 4-[4- (N,N-dimethylsulfamoyl)-piperazino]-2-methylpyrimidine, SDH-1, and its active metabolite 4-[4-(N,N-dimethylsulfamoyl)-piperazino]-2- hydroxymethylpyrimidine, SDH-2, suggest that inhibition of sorbitol dehydrogenase may be beneficial in delaying the onset of diabetic complications due to their ability to ameliorate redox changes associated with polyol metabolism. To compare the relative importance of sorbitol dehydrogenase versus aldose reductase inhibition on sugar cataract formation, cataract formation was monitored in 50{\%} galactose-fed and diabetic rats treated with/without the sorbitol dehydrogenase inhibitors SDH-1 or SDH-2 or the aldose reductase inhibitors AL 1576 or Ponalrestat. For these studies, diabetes was induced in young 50 g rats with streptozotocin while galactosemia was produced by feeding a diet containing 50{\%} galactose. Inhibitors were administered in the diet with the diet containing 0.06{\%} (w/w) of the sorbitol dehydrogenase inhibitors or Ponalrestat, and 0.0125{\%} (w/w) of AL 1576. Cataract formation was monitored by hand-held slit lamp and polyol levels were measured by gas chromatography. Sugar cataract formation was accelerated in diabetic rats treated with sorbitol dehydrogenase 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. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalysed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.",
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AU - Rodriguez, Libaniel

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