Inhibitory effects of grape seed proanthocyanidin extract on selenite-induced cataract formation and possible mechanism

Abstract

This study investigated the inhibitory effect of grape seed proanthocyanidin extract (GSPE) on selenite-induced cataract formation in rats and the possible mechanism. Eighty 8-day-old Sprague-Dawley rats were divided randomly into 5 groups: control group, model group, three GSPE groups (low dose, medium dose and high dose). Control group received subcutaneous injection of physiological saline. Model group was given subcutaneous injection of sodium selenite (20 μmol/kg body weight) on the postpartum day 10, and once every other day for consecutive three times thereafter. GSPE treated groups were respectively administered GSPE at doses of 50, 100, and 200 mg/kg body weight intragastrically 2 days prior to the selenite injection (that was, on the postpartum day 8), and once daily for fourteen consecutive days thereafter. The opacity of lenses was observed, graded and photographed under the slit lamp microscopy and the maximal diameter of the nuclear cataract plaques was measured. The lenses were analyzed for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), calcium (Ca(2+)), nitric oxide (NO) and anti-hydroxyl radical ability (anti-OH(-)). The histomorphology of lenses was observed with HE staining under a light microscope. The levels of calpainII, and iNOS protein and mRNA expression in lenses were detected by using immunohistochemistry and real-time quantitative RT-PCR. The results showed subcutaneous injection of sodium selenite led to severe nuclear cataract in model group, and the achievement ratio of model group was 100%. As compared with model group, the degree of lenses opacity and the maximal diameter of nuclear cataract plaques were significantly reduced in GSPE-treated groups. Moreover, we observed selenite treatment caused a significant decrease in the activities of antioxidative enzymes (SOD, CAT, GSH-PX) and anti-OH(-) ability, accompanied by a significant increase in the levels of MDA, NO, Ca(2+) as well as iNOS, and calpainII protein and mRNA expression. Administration of GSPE could dose-dependently preserve the activities of these antioxidative enzymes and anti-OH(-) ability, accompanied by a significant reduction in the levels of MDA, NO, Ca(2+) as well as iNOS, and calpainII protein and mRNA expression. These results suggested that GSPE markedly prevented selenite-induced cataract formation probably by suppressing the generation of lipid peroxidation and free radicals as well as the activation of iNOS, and calpainII in the lenses.