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Inhibitory effects of grape seed proanthocyanidin extract on selenite-induced cataract formation and possible
Xuan Zhang1,2, Yizhen Hu3
1Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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.
Insights
Grape seed proanthocyanidin extract (GSPE) effectively prevents selenite-induced cataracts in rats by reducing oxidative stress and inhibiting key enzymes. GSPE treatment preserves lens clarity and antioxidant enzyme activity, offering a potential therapeutic strategy for cataract prevention.
Area of Science:
- Ophthalmology
- Pharmacology
- Biochemistry
Background:
- Cataracts, particularly nuclear cataracts, represent a significant cause of vision impairment.
- Selenite-induced cataract in rats is a well-established animal model for studying cataractogenesis.
- Oxidative stress and specific enzyme pathways are implicated in the development of cataracts.
Purpose of the Study:
- To investigate the inhibitory effects of grape seed proanthocyanidin extract (GSPE) on selenite-induced cataract formation in a rat model.
- To elucidate the underlying mechanisms by which GSPE exerts its protective effects against cataract development.
Main Methods:
- Establishment of a selenite-induced cataract model in Sprague-Dawley rats.
- Administration of varying doses of GSPE (50, 100, 200 mg/kg) prior to and during selenite exposure.
- Assessment of lens opacity, measurement of antioxidant enzyme activities (SOD, CAT, GSH-PX), lipid peroxidation marker (MDA), calcium levels, nitric oxide, and hydroxyl radical scavenging ability.
- Histopathological examination of lens tissues and detection of calpain II and inducible nitric oxide synthase (iNOS) protein and mRNA expression.
Main Results:
- Selenite injection induced severe nuclear cataracts in 100% of the model group rats.
- GSPE treatment dose-dependently reduced lens opacity and the size of cataract plaques.
- GSPE administration preserved the activities of antioxidant enzymes (SOD, CAT, GSH-PX) and anti-hydroxyl radical ability, while decreasing MDA, nitric oxide, and calcium levels.
- GSPE significantly reduced the expression of calpain II and iNOS proteins and mRNA in the lenses.
Conclusions:
- Grape seed proanthocyanidin extract (GSPE) demonstrates significant efficacy in preventing selenite-induced cataracts in rats.
- The protective mechanism involves the suppression of lipid peroxidation, free radical generation, and the downregulation of iNOS and calpain II activation in the lens.
- GSPE holds potential as a therapeutic agent for preventing or treating cataracts.
