Naphthalene-induced cataract in the rat. II. Contrasting effects of two aldose reductase inhibitors on glutathione and glutathione redox enzymes.
This investigation compared the effects of two types of aldose reductase inhibitors on several biochemical parameters in naphthalene-induced cataract of the rat over a time span of 102 days of treatment. Feeding of naphthalene daily to brown Norway rats resulted in gradual, progressive development of zonular opacities. As compared to control animals, the values of soluble protein, soluble glutathione (total of oxidized plus reduced) and activities of glutathione peroxidase and glutathione reductase were decreased in rats fed either naphthalene or naphthalene + FK366, a carboxylic-acid-type aldose reductase inhibitor. In marked contrast, treatment with A11576, a hydantoin-type aldose reductase inhibitor, maintained the values of most parameters (with one exception) at levels that were similar to those of the controls, and all lenses remained clear. A decline of glutathione was noted in all naphthalene-fed rats, irrespective of whether these animals had been treated with an aldose reductase inhibitor. The great decrease of glutathione with A11576 suggests that this inhibitor acts at some step in naphthalene metabolism following formation of naphthalene epoxide.
Tao
R V
RV
Department of Ophthalmology, University of Illinois, Chicago.
Holleschau
A M
AM
Rathbun
W B
WB
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001835:Body Weight; D002386:Cataract / Q000139:chemically induced / Q000201:enzymology*; D004195:Disease Models, Animal; D005260:Female; D005449:Fluorenes / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D006827:Hydantoins / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology; D009281:Naphthalenes; D009929:Organ Size; D011799:Quinazolines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN
D005449:Fluorenes; D006827:Hydantoins; D009281:Naphthalenes; D011799:Quinazolines; C052241:imirestat; C064920:FR 74366; C031721:naphthalene; D000449:Aldehyde Reductase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione