Delay of cataract development in hereditary cataract UPL rats by disulfiram and aminoguanidine.
The UPL rat is a newly developed hereditary cataract model. We previously found that the administration of disulfiram, a dimer of diethyldithiocarbamate that possesses antioxidant activity, and aminoguanidine, which is known to inhibit inducible nitric oxide synthase, inhibits cataract development in selenite-induced cataract rats. In this study, we investigated the anti-cataract effects and mechanism of disulfiram and aminoguanidine on UPL rats. The opacities of UPL rat lenses, as documented by the anterior eye segment analysis system, EAS-1000 (Nidek, Aichi, Japan), increased from 39 days, and apparently mature cataracts were observed at 53 days. Accompanied with the increase in lens opacity, glutathione concentrations in UPL rat lenses decreased. The Na(+) to K(+) and water-insoluble to water-soluble protein ratios, as well as the Ca(2+) contents in UPL rat lenses increased with the development of cataracts. Oral administration of disulfiram and aminoguanidine delayed the lens opacification as well as the changes in glutathione, Na(+) to K(+) ratio, water-insoluble to soluble protein ratio, and Ca(2+) content in UPL rat lenses. The opacity and Ca(2+) content of UPL rat lenses were closely associated. The present study demonstrates that disulfiram and aminoguanidine have potency of the delay of cataract development in UPL rats, probably caused by inhibiting the rise in Ca(2+) levels.
Nabekura
Tomohiro
T
School of Pharmaceutical Sciences, Kinki University, Kowakae, Higashi-Osaka, Osaka 577-8502, Japan. nabe@phar.kindai.ac.jp
Koizumi
Yuichi
Y
Nakao
Motoki
M
Tomohiro
Masayuki
M
Inomata
Mitsushi
M
Ito
Yoshimasa
Y
D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D002386:Cataract / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D003459:Crystallins / Q000378:metabolism; D004221:Disulfiram / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D015785:Eye Diseases, Hereditary / Q000378:metabolism / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D006146:Guanidines / Q000627:therapeutic use*; D007908:Lens, Crystalline / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D003459:Crystallins; D004791:Enzyme Inhibitors; D006146:Guanidines; D019001:Nitric Oxide Synthase; D005978:Glutathione; C004479:pimagedine; D002118:Calcium; D004221:Disulfiram