Selenite-induced Cataractogenesis Research Articles

Effects of Laurus Nobilis Eye Drop on Selenite-Induced Cataract Formation and Oxidative Stress-Related Parameters in Rabbits: An Experimental Study

Purpose To evaluate the protective role of Laurus Nobilis eye drops on selenite-induced cataracts in suckling rabbits. Methods Fifteen male albino suckling rabbits with no signs of ocular inflammation were randomly assigned to three groups: controls (Group A), sodium-selenite group (Group B) and sodium-selenite plus Laurus Nobilis group (Group C). By selenite treatment, cataract formation was experimentally induced and then graded. The grade of oxidative stress was defined in the lens, measuring the concentration of malondialdehyde, alpha-tocopherol, oxidized glutathione, ascorbic acid and hydrogen peroxide, and in blood samples as levels of alpha-tocopherol and malondialdehyde. Results Mean lens concentrations of GSSG, H2O2, and MDA levels in group B were significantly higher than in both group C and control. Ascorbic acid and alpha-tocopherol concentrations were lower in group B than in both group C and A. As plasma oxidative status markers, the level of MDA was higher in group B respected group C and A. The mean alpha-tocopherol levels in group B were significantly lower than in both group A and group C. Conclusions In animals treated with Laurus Nobilis-based eye drops, inflammation was inhibited, and lipid peroxidation was significantly reduced. Laurus nobilis leaves extract represents a good source of antioxidant components that may contrast sodium selenite-induced cataractogenesis in suckling rabbits.

Potential therapeutic effect of Salvia coccinea leaf extract in chronic disorders: Myocardial infarction, cataract, and arthritis in rat

Aqueous extract from Salvia coccinea leaf (AESL) has been shown its unique anti-oxidant effect via Nuclear factor (NF)-kappa (κ)B pathway in human monocytic THP-1 ​cells and pharmacological effect on inflammatory diseases like diabetes in rats. Using AESL, which possess antioxidant activity by scavenging radicals and decreasing oxidative stress, would be a promising strategy for the treatment of other inflammatory disorders like myocardial infarction, arthritis, and cataract. This study was designed to evaluate the ameliorating effects of AESL on isoproterenol (Iso)-induced myocardium infarction (MI), selenite-induced cataractogenesis, and complete Freund's adjuvant-induced arthritis in Wistar rats. In this study, AESL ameliorated pathological changes in Iso-induced MI heart muscles and Electro Cardio Gram pattern, 35–80 ​% protection of the cataractogenesis, and prevented the apoptosis induced by selenite in the rat lens. Both pre and post-treatment of AESL (600 ​mg/kg, bw) showed no swelling of the joint and, 35 days treatment showed significant prevention against bony destruction as depicted by less narrowing of joint spaces and soft tissue swelling when compared with control rats. Oral administration of AESL inhibited the Iso-induced increase in serum and myocardial lipid peroxidation, aspartate transaminase, alanine transaminase, creatine kinase, troponin-I, and troponin-T, and lactate dehydrogenase of myocardium infarction rats. Significant increases in the activity of superoxide dismutase, catalase, glutathione peroxidase, and a reduced level of glutathione, were observed in AESL treated cataract rat lens. The results demonstrate that AESL is useful in, in addition to diabetes, controlling myocardium infarction, cataracts, and arthritis.

The Aqueous Stem Bark Extract of Alstonia boonei Exhibits Anticataract Activity in Sprague Dawley Rat.

In Africa, Alstonia boonei is used folklorically for the management of the multitude of conditions including cataract, which accounts for 50% of cases of blindness in the region. The current study set out to probe the traditional use of the aqueous extract of Alstonia boonei stem bark (ABE) as an anticataract remedy using Sprague Dawley rat models. We investigated the probable phytochemical constituents in the extract, in vitro antioxidant potential, and its in vitro aldose reductase inhibition. For the anticataract investigations, diabetic cataract was induced using galactose in 3-week-old Sprague Dawley rats, and age-related cataract was induced by the administration of sodium selenite to 10-day-old rat pups. Cataract scores in both models were determined after treatment with 30, 100, and 300 mgkg-1 doses of ABE and 10 mlkg-1 of distilled water. Lens glutathione, total lens protein, soluble lens proteins (alpha-A) crystallin, and aquaporin 0 levels in the enucleated lens homogenates were determined. Changes in lens to body weight were also determined with histopathological analysis done on the lenses in the selenite-induced cataract model. The presence of alkaloids, tannins, flavonoids, glycosides, and triterpenoids was identified in the extract. The extract inhibited aldose reductase activity with IC50 of 92.30 μgml-1. The 30, 100, and 300 mgkg-1ABE-treated rats recorded significantly (p < 0.05) reduced cataract scores indicating a delay in cataractogenesis in galactose-induced cataract and in selenite-induced cataractogenesis as well. Markers of lens transparency such as AQP0, alpha-A crystallin, and total lens proteins and lens glutathione levels were significantly (p < 0.05) preserved. In conclusion, this study establishes the anticataract potential of the aqueous stem bark extract of Alstonia boonei in Sprague Dawley rat models.

Anticataract Effect of the Aqueous Extract of the Flowers of Aspilia africana in Murine Model of Diabetic and Age-Related Cataracts.

The use of Aspilia africana in traditional medicine for the management of ocular diseases has been reported in India and some indigenous communities of Africa. The aim of this study was to investigate the aqueous extract of the flowers of A. africana (AAE) as an anticataract remedy using murine models of diabetic and senile cataracts. Preliminary phytochemical screening of the extract, in vitro antioxidant assays, and in vitro aldose reductase inhibitory activity were performed. For anticataract investigations of the extracts, diabetic cataract was induced by galactose administration in 3-week-old Sprague Dawley rats. The evaluation of experimentally induced age-related cataract was performed by administering sodium selenite to 10-day-old rat pups. The phytochemical analysis revealed the presence of alkaloids, tannins, flavonoids, glycosides, and saponins. In vitro aldose reductase inhibitory property of the extract on rat lenses revealed that the AAE inhibited the enzyme activity with IC50 of 12.12 µg/ml. For the anticataract investigations, 30, 100, and 300 mg·kg-1AAE-treated rats recorded significantly low (p ≤ 0.0001) cataract scores compared to the negative control rats, indicating a delay in cataractogenesis from the second week of treatment in the galactose-induced cataractogenesis. Similarly, the treatment with AAE caused a significant reduction (p ≤ 0.0001) in cataract scores compared to the negative control rats in the selenite-induced cataractogenesis. Markers of lens transparency, such as aquaporin 0, alpha-A crystallin, and total lens proteins and lens glutathione levels, were significantly preserved (p ≤ 0.05-0.0001) in each cataract model after AAE treatment. The study established the anticataract potential of the aqueous extract of flowers of A. africana in murine models, hence giving scientific credence to its folkloric use in the management of cataract.

A comparison between plain eugenol and eugenol-loaded chitosan nanoparticles for prevention of in vitro selenite-induced cataractogenesis

The purpose of this work was to improve the antioxidant and anticataractogenic potential of eugenol by encapsulating it within chitosan nanoparticles via an emulsion–ionic gelation crosslinking method. Various ratios of chitosan to eugenol (1:0.75, 1:1 and 1:1.25) were optimized by encapsulation efficiency, loading capacity, drug-releasing profile, and in-vitro antioxidant potential. Synthesized eugenol-loaded chitosan nanoparticles (ECNP 1:1) and plain chitosan nanoparticles (CNPs) were characterized by UV–visible spectrometry, dynamic light scattering (DLS), X-ray powder diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and atomic force microscopy (AFM). The range of sizes of ECNPs, as determined by the AFM and DLS methods, was approximately 200–600 nm. 3–4,5-(dimethyl-thyazol-2-yl)-2,5-diphenyltetrazolium (MTT) analysis revealed that ≥ 50% of cultured human lenticular epithelial (HLE-B3) cells remained viable when exposed to an ECNP concentration of 150 μM or less. These ECNPs were evaluated for efficacy in preventing experimental in-vitro selenite-induced cataractogenesis. Encapsulation of eugenol within chitosan nanoparticles appeared to improve the antioxidant capacity of plain eugenol; this could conceivably improve the anticataractogenic potential of eugenol.

Molecular Basis of Preventive Effects of Habitual Coffee Intake against Chronic Diseases

Epidemiological studies have shown that coffee consumption may be associated with a lower risk of developing several chronic disorders. To elucidate the molecular mechanism of the effects of coffee, we analyzed molecular response upon exposure to coffee extract using cellular and animal models of these diseases. As obesity is recognized as a major risk factor for these chronic diseases, we investigated the effect of coffee on adipogenesis using mouse preadipocyte 3T3-L1 cells. We found that coffee induced proteasomal degradation of IRS-1, leading to reduction of PPARγ expression, a master transcription factor for adipogenesis. Reduction in weight as well as in IRS-1 expression was detected in the fat tissues of the high fat-diet-fed mice when reared with 60% coffee for 7 weeks. As for Alzheimer's disease, we analyzed the effect of coffee on amyloid β (Aβ) production in human neuronal SH-SY5Y cells. We found a 20% reduction in Aβ production when treated with 2.5% coffee for 2 d. This reduction was due to proteasomal degradation of BACE1 (β-secretase), which was activated by protein kinase A. In addition, coffee ameliorates LPS-induced inflammatory responses in RAW264.7 macrophages by reducing NFκB activity and Nrf2 activation. Roasted coffee prevents selenite-induced cataractogenesis by ameliorating antioxidant loss. Pyrocatechol, a component of roasted coffee, also reduced Aβ production and exhibits anti-inflammatory effects by a similar mechanism as coffee. Our results suggest that roasting coffee beans to generate pyrocatechol is necessary for the preventive effects of coffee intake on the chronic diseases.

The Preventive Effects of Asparagus officinalis Extract on Sodium Selenite-Induced Cataractogenesis in Experimental Animal Models.

Materials and Methods Neonatal rats received a single dose of sodium selenite as an intraperitoneal injection (30 μmol/kg) on day 10 postnatal to induce cataract. Animals were then posttreated with various oral solutions of A. officinalis extract at 200 mg/kg or 400 mg/kg once daily on days 10–16 postnatal. Cataract was evaluated by slit-lamp, and lens opacification was analyzed in each group 24 hours after the last treatment at day seven postadministration of the extracts or vehicle. The total protein concentration of lenses, glutathione reductase activity as the glutathione antioxidant capacity, and malondialdehyde content as a marker of lipid peroxidation were further assessed in removed rat lenses on day 30 postnatal. Results All lenses in the healthy and control plant groups were clear. Sodium selenite significantly increased cataract grade (2.8 ± 0.2) when compared to the healthy group (p = 0.001). However, cataract grades were decreased considerably as 1.9 ± 0.72 and 1.5 ± 0.85 in groups that received 200 mg/kg and 400 mg/kg oral extract of A. officinalis, respectively. A. officinalis extract also restored all abnormalities of biochemical markers induced by sodium selenite. Conclusion Our data suggest that A. officinalis could be a promising candidate as a safe alternative treatment in cataracts upon further clinical trials. This effect is probably associated with the antioxidant activity of A. officinalis.

Comparison of the efficacy of a Tabernaemontana divaricata extract and of biosynthesized silver nanoparticles in preventing cataract formation in an in-vivo system of selenite-induced cataractogenesis

Abstract The putative anticataractogenic efficacy of silver nanoparticles (AgNPs), biosynthesized with a Tabernaemontana divaricata (T. divaricata) extract, was evaluated in-vivo in four groups of Wistar rat pups: Group I (normal [control]); Group II (selenite-challenged [19 μmol/kg body weight], untreated); Group III (selenite-challenged, T. divaricata extract-treated [350 mg/kg body weight]); and Group IV (selenite-challenged, biosynthesized AgNPs-treated [200 mg/kg body weight]). Mean levels/activities of lenticular reduced glutathione (GSH), malondialdehyde (MDA), calcium, Ca2+ and Na+/K+-ATPase and total calpain were measured. The expression pattern of genes at mRNA transcript (by reverse transcription-PCR) and protein (by immunoblot analysis) levels for Ca2+ transporters, calpain isoforms and lenticular proteins (αA- and βB1-crystallins, and vimentin) were evaluated. In extract-treated and AgNPs-treated rats, relatively higher mean lenticular levels/activities of GSH, Ca2+ and Na+/K+-ATPase, total calpain, and higher mRNA transcript and protein levels of calpain isoforms and lenticular proteins were observed. However, relatively lower mean lenticular levels of MDA, calcium and also mRNA transcript and protein levels of plasma membrane Ca2+-ATPase-1 (PMCA-1) and sarco/endoplasmic reticulum Ca2+-ATPase-2 (SERCA-2) were recorded. The prevention of such lenticular alterations was more pronounced in AgNPs-treated rats than in plain extract-treated rats. These observations suggest that AgNPs biosynthesized with T. divaricata extract have the potential to prevent selenite-induced cataractogenesis in-vivo by maintaining normal lenticular calcium homeostasis and calpain cascade activities and by preventing alterations in key lenticular proteins.

Evaluation of the Putative Efficacy of a Methanolic Extract of Ocimum Basilicum in Preventing Disruption of Structural Proteins in an in Vitro System of Selenite-induced Cataractogenesis

ABSTRACTPurpose: To evaluate whether a methanolic extract of Ocimum basilicum (OB) leaves prevented lenticular protein alterations in an in-vitro model of selenite-induced cataractogenesis.Materials and Methods: Transparent lenses extirpated from Wistar rats were divided into three groups: control; selenite only; treated. Control lenses were cultured in Dulbecco’s modified Eagle’s medium (DMEM) alone, selenite only lenses were cultured in DMEM containing sodium selenite only (100 µM selenite/ml DMEM) and treated lenses were cultured in DMEM containing sodium selenite and the methanolic extract of OB leaves (200 µg of extract/ml DMEM); all lenses were cultured for 24 h and then processed. The parameters assessed in lenticular homogenates were lenticular protein sulfhydryl and carbonyl content, calcium level, insoluble to soluble protein ratio, sodium dodecyl sulphate-polyacrylamide gel electrophoretic (SDS-PAGE) patterns of lenticular proteins, and mRNA transcript and protein levels of αA-crystallin and βB1-crystallins.Results: Selenite only lenses exhibited alterations in all parameters assessed. Treated lenses exhibited values for these parameters that were comparable to those noted in normal control lenses.Conclusions: The methanolic extract of OB leaves prevented alterations in lenticular protein sulfhydryl and carbonyl content, calcium level, insoluble to soluble protein ratio, SDS-PAGE patterns of lenticular proteins, and expression of αA-crystallin and βB1-crystallin gene and proteins in cultured selenite-challenged lenses. OB may be further evaluated as a promising agent for the prevention of cataract.

Protective Effects of Rosmarinic Acid against Selenite-Induced Cataract and Oxidative Damage in Rats.

Cataracts are the major cause of blindness and are associated with oxidative damage of the lens. In the present study, the aim was to evaluate the protective effects of rosmarinic acid on selenite-induced cataractogenesis in Sprague-Dawley rat pups. The animals were randomly divided into five groups, each of which consisted of 10 rat pups. Group I served as normal control (vehicle administration). For testing cataract induction, animals of Groups II, III, IV, and V were administered a single subcutaneous injection of sodium selenite (2.46 mg/kg body weight) on postpartum day 12. After sodium selenite intoxication, Group II served as control selenite. From the 11th day through the 17th day, Groups III-V received rosmarinic acid intraperitoneally at doses of 5, 10, and 50 mg/kg, respectively. On postpartum day 24, the rat pups were examined for cataract formation, and the lenses were isolated for further analysis of proteins and oxidative damage indicators. Selenite caused significant (p < 0.05) cataract formation. Through the effects of selenite, the protein expressions of filensin and calpain 2 were reduced, and the calcium concentrations, the level of lipid peroxidation (TBARS), and inflammation indicators (iNOS, COX-2, and NFκB) were upregulated. Furthermore, the protein expression of the antioxidant status (Nrf2, SOD, HO-1, and NQO1), the antioxidant enzymes activities (GSH-Px, GSH-Rd, and catalase), and the GSH levels were downregulated. In contrast, treatment with rosmarinic acid could significantly (p < 0.05) ameliorate cataract formation and oxidative damage in the lens. Moreover, rosmarinic acid administration significantly increased the protein expressions of filensin, calpain 2, Nrf2, SOD, HO-1, and NQO1, the antioxidant enzymes activities, and the GSH level, in addition to reducing the calcium, lipid peroxidation, and inflammation indicators in the lens. Taken together, rosmarinic acid is a prospective anti-cataract agent that probably delays the onset and progression of cataracts induced by sodium selenite.

In vitro antioxidant and anticataractogenic potential of silver nanoparticles biosynthesized using an ethanolic extract of Tabernaemontana divaricata leaves.

Silver nanoparticles (AgNPs) have been found useful in biological systems and in medicine since they possess a large surface area to volume ratio, which confers on them several unique properties. In the present study, AgNPs that had been biosynthesized using an ethanolic extract of Tabernaemontana divaricata leaf were evaluated for putative antioxidant potential and efficacy in preventing experimental in-vitro selenite-induced opacification of the ocular lens (cataractogenesis). The antioxidant potential of the AgNPs was evaluated in-vitro by looking for radical-scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) free radicals as well as by determining reducing power. The anticataractogenic potential of the AgNPs was evaluated in an in-vitro model of selenite-induced cataractogenesis in five groups of Wistar rat lenses cultured in Dulbecco's modified Eagle's medium (DMEM) for 24h: Group I lenses (negative control) were cultured in DMEM alone; Group II lenses were exposed to sodium selenite alone (100μM); Group III lenses were exposed simultaneously to sodium selenite and the T. divaricata extract (250μg/ml); Group IV lenses were exposed simultaneously to sodium selenite and the biosynthesized AgNPs (125μg/ml); and Group V lenses were exposed to the AgNPs alone. In these lenses, gross morphological changes, as well as activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and levels of reduced glutathione (GSH) and malondialdehyde (MDA), were determined. In-vitro, the AgNPs (which were spherical in shape with an average diameter ranging from 15 to 50nm) showed potent and concentration-dependent radical-scavenging activity on DPPH and H2O2 free radicals as well as reducing power. The gross morphological changes seen in the cultured rat lenses were: all eight control (Group I) lenses remained transparent; dense opacification was noted in all eight selenite-challenged untreated (Group II) lenses; in selenite-challenged, simultaneously T. divaricata extract-treated (Group III) lenses, no opacification occurred in seven of eight (87.5%) lenses and only minimal opacification in one (12.5%) lens; all the eight Group IV (selenite-challenged, simultaneously AgNPs-treated) lenses did not show any opacification; and all the eight Group V lenses (exposed to AgNPs alone) remained as transparent as control lenses. The mean activities of CAT, SOD, GPx and GST, and the mean levels of GSH, were significantly (p<0.05) lower in Group II lenses than those in Groups I, III, IV and V lenses, while the mean MDA level was significantly (p<0.05) higher in Group II lenses than those in Groups I, III, IV and V lenses; oxidative damage possibly occurred in Group II lenses, whereas this appears to have been prevented in Groups III and IV lenses. These observations suggest that the T. divaricata leaf ethanolic extract, and also the AgNPs biosynthesized using the T. divaricata extract, possess effective in-vitro antioxidant activity and the potential to prevent experimental selenite-induced opacification in cultured Wistar rat lenses.

Luteolin Supplementation Prevents Selenite-Induced Cataractogenesis in Sprague Dawley Rat Pups.

Luteolin, a flavonoid present in leaves and stems of many plants finds mention in literature for beneficial effects on eyes. Presently, no reports are available on the in vivo anticataractogenic effect of luteolin. The current study was designed to evaluate the efficacy of luteolin on selenite-induced cataract models in vivo. The study consisted of three groups of Sprague Dawley rat pups 8-10 d old (Group I (Normal), Group II (Cataract induced), and Group III (Treatment)). Cataract was induced in Group II and Group III by a subcutaneous injection of sodium selenite (4 μg/g body weight) on the 10th day. Luteolin was administered orally from 8th day up to 12th day at a concentration of 1 μg/g body weight in Group III. After 30 d, lenses of treated animals showed normal morphology. Activities of antioxidant enzymes were increased and levels of reactive oxygen species were decreased in the luteolin-treated group when compared to the cataract-induced group. Increased Ca(2+) ATPase activity and lowered calcium level, caspase 3 activity and down-regulation of caspase 3 expression were seen in the treatment group when compared to the selenite group. Luteolin enhances the antioxidant potential and thereby lowers the oxidative damages to the lens. It also stabilizes the membrane integrity of the lens and maintains the ionic balance.

Prevention of selenite-induced cataractogenesis by hydroalchoholic extract of Echium amoenum: An experimental evaluation of the Iranian traditional eye medication

Prevention of selenite-induced cataractogenesis by hydroalchoholic extract of Echium amoenum: An experimental evaluation of the Iranian traditional eye medication

Structure-Based Virtual Screening and Biological Evaluation of a Calpain Inhibitor for Prevention of Selenite-Induced Cataractogenesis in an in Vitro System.

Calpains belong to the family of calcium-dependent, structurally related intracellular cysteine proteases that exhibit significant functions in evolution of different types of cataracts in human as well as animal models. Application of calpain inhibitors generated through a virtual screening workflow may provide new avenues for the prevention of cataractogenesis. Hence, in the current study, compounds were first screened for potent calpain inhibitory activity by employing a structure-based approach, and the screening results were then validated through biological experiments in rat lenses. A hit compound, HTS08688, was obtained by structure-based virtual screening. A micromolar concentration of HTS08688 was found to prevent in vitro cataractogenesis in isolated Wistar rat lenses, while maintaining the antioxidant and calcium concentrations at near normal levels. Inhibition of superoxide anion generation, as observed through cytochemical localization studies, and maintenance of structural integrity, as demonstrated by histological analysis of lenticular tissue, also suggested that HTS08688 can ameliorate the cataractous condition induced by selenite in an in vitro rodent model. A cell proliferation assay was performed; the IC 50 value of the screened calpain inhibitor, HTS08688, against human lenticular epithelial cells-b3 was found to be 177 μM/mL. This combined theoretical and experimental approach has demonstrated a potent lead compound, HTS08688, that exhibits putative anticataractogenic activity by virtue of its potential to inhibit calpain.

Prevention of Selenite-Induced Cataratogenesis by Ginkgo biloba Extract (Egb761) in Wistar Rats

Objective: To investigate whether Ginkgo biloba extract retards selenite-induced cataractogenesis in Wistar rat pups.Methods: On postpartum day eight, Group I rat pups (n = 12) received an intraperitoneal injection of physiological saline. Groups II and III rat pups (n = 12) received a subcutaneous injection of sodium selenite. Group III also received an intraperitoneal injection of G. biloba extract once daily on postpartum days 9–14. Both eyes of each pup were examined from postpartum day 16 up to day 30. After sacrifice, encapsulated pup lens were analyzed for mean activities of catalase, superoxide dismutase, glutathione peroxidase (GPx), glutathione S-transferase and glutathione reductase. In addition, the mean concentrations of reduced glutathione (GSH) and malondialdehyde were analyzed in samples of lens and serum.Results: Dense lenticular opacification occurs 100% in Group II, but only minimal opacification occurs in three pups of Group III (25%), no opacification in 75% of Group III, none in Group I. Compared with Groups I and III, Group II rat showed lower lenticular antioxidant enzyme activity, lower level of GSH, and higher level of malondidehyde (mean ± standard deviation SD, p < 0.05 respectively).Conclusions: The treatment with G. biloba extract is effective against oxidative stress – a crucial factor of cataractogenesis in rat pups, possibly by preventing depletion of antioxidant enzymes and by inhibiting lipid peroxidation.

178 - Reversing Selenite-Induced Cataractogenesis in Rats by N-Acetylcysteineamide Eye Drops

178 - Reversing Selenite-Induced Cataractogenesis in Rats by N-Acetylcysteineamide Eye Drops

Ameliorative effect of acetyl-l-carnitine and/or nifedipine against selenite-induced cataractogenesis in young albino rats

Free radical toxicity and calcium ion overload have been identified as the major two players in the causation of cataract. The current study was carried out to investigate the anti-cataractogenic effect of single and combined treatment with acetyl-l-carnitine and nifedipine in sodium selenite-induced cataract. Rat pups were divided into 5 groups; 1st group received intraperitoneal injection (i.p.) of saline and served as normal control, 2nd group received single subcutaneous injection of sodium selenite 30nmol/g body weight on p10 (postpartum day 10), 3rd and 4th groups received either acetyl-l-carnitine (200mg/kg, i.p.) or nifedipine (0.1mg/kg, i.p.) on p9, respectively, before the administration of sodium selenite, and the treatment continued till p14. Last group received the combined treatments of acetyl-l-carnitine and nifedipine in the same regimen. All animals were examined using a slit lamp and retroillumination then sacrificed on p30. Lenses were removed and processed for biochemical analyses, histopathological and electron microscopic examination. Selenite-treated groups showed significantly (P≤0.05) lower values of redox system components (glutathione and glutathione reductase activity) and anti-oxidant enzymes׳ activities (superoxide dismutase and catalase) along with increased lipid peroxidation that was accompanied by 100% opacified crystalline lenses (mature cataract) with abnormal structure as detected by electron microscopy. It is concluded that acetyl-l-carnitine or nifedipine was able to partially protect against selenite-induced abnormalities. While, combined treatment with acetyl-l-carnitine and nifedipine was superior to individual treatments in slowing down the development of cataract by restoring the anti-oxidant defense and mitigating lipid peroxidation in the lens and hence represents an attractive anti-cataractogenic remedy.

C-Phycocyanin Modulates Selenite-Induced Cataractogenesis in Rats

The present investigation is aimed to evaluate the anticataractogenic potential of C-phycocyanin (C-PC), extracted and purified from Spirulina platensis. Enucleated rat lenses were maintained in vitro in Dulbecco's modified Eagle medium (DMEM). Group I contained DMEM, Group II and Group III contained 100μM of sodium selenite, Group III was subdivided into three viz IIIa, IIIb, IIIc supplemented with 100, 150, 200μg of C-PC respectively. In the in vivo study, on tenth day post partum: Group I rat pups received an intraperitoneal injection of saline, Group II, IIIa, IIIb, and IIIc rat pups received a subcutaneous injection of sodium selenite (19μmol/kg bodyweight) Group IIIa, IIIb, IIIc also received an intraperitoneal injection of 100, 150, 200mg/kg body weight of C-PC, respectively, from postpartum days 9-14. On termination of the experiment, the lenses from both in vitro and in vivo studies were subjected to morphological examination and subsequently processed to estimate the activities of antioxidant enzymes namely superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, levels of reduced glutathione and lipid peroxidation products. Sodium selenite-exposed, C-PC-treated rat lenses (Group IIIc), showed significant restoration of antioxidant enzyme activity (p < 0.05) when compared to their counterpart Group II. Group IIIc conserved the levels of GSH and lipid peroxidation products at near to normal levels as compared with Group II. Results conclude the possible role of C-PC in modulating the antioxidant enzyme status, thereby retarding sodium selenite-induced cataract incidence both in vitro and in vivo.

Alterations in the lenticular protein profile in experimental selenite-induced cataractogenesis and prevention by ellagic acid

Accumulating evidence suggests that oxidative stress underlies age-related formation of cataract, and that antioxidants retard cataractogenesis. This study aimed to evaluate whether ellagic acid, a natural polyphenol with antioxidant properties, prevents alterations in the lenticular protein profile in an experimental model of selenite cataract. Alterations in lenticular protein were determined by two-dimensional electrophoresis (2DE) and image analysis. Eluted αA-crystallin spots were analyzed by mass spectrometry. Western blot analysis was also performed to confirm the differential expression of certain crystallins and cytoskeletal proteins. In cataractous lenses, 2DE and image analysis revealed approximately 45 and 60 prominent spots in soluble and insoluble protein fractions respectively. Analysis of the pI and molecular weight of protein spots revealed differences in the expression of crystallin proteins in soluble and insoluble fractions. Western blot analysis confirmed changes in the expression of αA- and βB1- crystallins in both soluble and insoluble protein fractions, while mass spectrometry confirmed the degradation of αA-crystallin in selenite cataractous lenses. Western blot analysis also confirmed the occurrence of altered expression of certain cytoskeletal proteins in insoluble fractions. However, the lenticular protein profile in lenses from selenite-challenged, ellagic acid-treated rats was essentially similar to that noted in lenses from normal rats. The present study confirms the importance of structural and cytoskeletal proteins in the maintenance of lenticular transparency; the results also suggest that ellagic acid prevents lenticular protein alterations induced by selenite in an experimental setting.

Prevention of Selenite-Induced Cataractogenesis by an Ethanolic Extract of Cineraria maritima: An Experimental Evaluation of the Traditional Eye Medication

In the present study, the antioxidant potential of an ethanolic extract of Cineraria maritima and its efficacy in preventing selenite-induced cataractogenesis were assessed in vitro and in vivo. In the in vitro phase of the study, lenses dissected out from the eyes of Wistar rats were incubated for 24 h at 37 °C in Dulbecco's modified Eagle medium (DMEM) alone (group I), in DMEM containing 100 μM of selenite only (group II), or in DMEM containing 100 μM of selenite and 300 μg/ml C. maritima extract added at the same time (group III). Gross morphological examination of the lenses revealed dense opacification in group II, minimal opacification in group III, and no opacification in group I lenses. The mean activities of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase were significantly lower in group II than in group I or group III lenses, while malondialdehyde concentration was significantly higher in group II lenses than in group I and group III lenses. In the in vivo phase of the study, dense opacification of lenses was noted in all rat pups (100%) that had received a single subcutaneous injection of sodium selenite alone (19 μM/kg body weight) on postpartum day 10, whereas cataract formation occurred in only 33.3% of rat pups that had received selenite as well as an intraperitoneal injection of the extract of C. maritima (350 mg/kg body weight) for five consecutive days. These observations suggest that the ethanolic extract of C. maritima may prevent experimental selenite-induced cataractogenesis.