Effect of disulfiram eye drops on lipid peroxide formation via excessive nitric oxide in lenses of hereditary cataract ICR/f rats.
The ICR/f rat is a recessive-type hereditary cataractous strain, and opacity in the lens usually becomes evident at around 75 d of age. We previously found that the instillation of eye drops containing a disulfiram and hydroxypropyl-beta-cyclodextrin inclusion complex (DSF eye drops) delays lens opacification in ICR/f rats. In this study, we attempted to clarify the mechanisms of the delaying effect of DSF eye drops on cataract development in ICR/f rats. The calcium ion (Ca2+) content in the lenses of ICR/f rats increases at 77 d of age, and this elevation is preceded by a decrease in Ca2+-ATPase activity. On the other hand, the levels of nitric oxide (NO) and lipid peroxide (LPO) also increase in the lenses of ICR/f rats at 63 d of age, while the lenses are still transparent. The instillation of DSF eye drops reduces the changes in Ca2+ content, Ca2+-ATPase activity, NO and LPO levels in the lenses of ICR/f rats. The present study demonstrates that excessive NO production induces the increase in LPO, which causes the decrease in Ca2+-ATPase activity, and the increase in Ca2+ content in the lenses of ICR/f rat during cataract development. DSF eye drops have the ability to attenuate the increase in the NO and LPO levels, resulting in a delay in cataract development.
Nagai
Noriaki
N
School of Pharmaceutical Sciences, Kindai University, Higashi-Osaka, Osaka 577-8502, Japan.
Ito
Yoshimasa
Y
Takeuchi
Noriko
N
D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002386:Cataract / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D003505:Cyclodextrins / Q000737:chemistry; D004221:Disulfiram / Q000008:administration & dosage / Q000494:pharmacology*; D005136:Eye Proteins / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009883:Ophthalmic Solutions; D051381:Rats
D000427:Alcohol Deterrents; D003505:Cyclodextrins; D005136:Eye Proteins; D008054:Lipid Peroxides; D009883:Ophthalmic Solutions; D009569:Nitric Oxide; D000252:Calcium-Transporting ATPases; D002118:Calcium; D004221:Disulfiram