Prevention of naphthalene-1,2-dihydrodiol-induced lens protein modifications by structurally diverse aldose reductase inhibitors

Sanai Sato, Katsumi Sugiyama, Yong S. Lee, Peter F. Kador

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The effects of aldose reductase inhibitors on lens protein modifications induced by naphthalene-1,2-dihydrodiol were investigated in vitro to confirm the role of aldose reductase on naphthalene cataract formation. HPLC analysis of naphthalene-1,2-dihydrodiol incubated with aldose reductase and NAD+ indicated the formation of a metabolite peak corresponding to 1,2- naphthoquinone. Soluble proteins from rat lenses prepared by gel filtration of crude lens extracts through Sephadex PD-10, incubated with naphthalene- 1,2-dihydrodiol in the presence of NAD+ displayed an absorbance ca 450 nm and their spectra were essentially identical to those of 1,2-naphthoquinone- protein adducts. Similar spectra were also obtained from proteins isolated from the intact rat lens after in vitro incubation in medium containing naphthalene-1,2-dihydrodiol. The spectra obtained from lens proteins incubated with 1,2-dihydroxynaphthalene were distinct from those of either naphthalene-1,2-dihydrodiol or 1,2-naphthoquinone. Aldose reductase inhibitors possessing either hydantoin or carboxylic acid groups prevented protein modification induced by naphthalene-1,2-dihydrodiol but not protein modification induced by 1,2-dihydroxynaphthalene or 1,2-naphthoquinone. Therefore, the metabolite formed from naphthalene-1,2-dihydrodiol by aldose reductase is 1,2-naphthoquinone. Lens proteins modified by naphthalene-1,2- dihydrodiol appear essentially identical to protein adducts formed with 1,2- naphthoquinone and their formation can be prevented by both hydantoin and carboxylic acid containing aldose reductase inhibitors.

Original languageEnglish (US)
Pages (from-to)601-608
Number of pages8
JournalExperimental Eye Research
Issue number5
StatePublished - May 1999
Externally publishedYes


  • Aldose reductase
  • Cataract
  • Lens
  • Naphthalene
  • Rat

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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