Prevention of naphthalene-1,2-dihydrodiol-induced lens protein modifications by structurally diverse aldose reductase inhibitors.
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.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D002386:Cataract / Q000209:etiology* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003459:Crystallins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005449:Fluorenes / Q000737:chemistry; D006827:Hydantoins / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D009281:Naphthalenes / Q000737:chemistry; D009284:Naphthols / Q000737:chemistry / Q000494:pharmacology*; D009285:Naphthoquinones / Q000737:chemistry; D010793:Phthalazines / Q000737:chemistry; D051381:Rats; D013053:Spectrophotometry