Effect of disulfiram eye drops on lipid peroxide formation via excessive nitric oxide in lenses of hereditary cataract ICR/f rats

Abstract

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-β-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. © 2008 Pharmaceutical Society of Japan.