Lens Of Diabetic Rats Research Articles

KLF5/MDM2 Axis Modulates Oxidative Stress and Epithelial-Mesenchymal Transition in Human Lens Epithelial Cells: The Role in Diabetic Cataract

Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The expression patterns of KLF5 were detected in vivo and in vitro. Then, KLF5 was knocked down in human lens epithelial cells (HLECs) to explore its functional roles and underlying mechanisms. Dual-luciferase reporter assay and chromatin immunoprecipitation analysis were used to detect whether KLF5 could bind the promoter of E3 ubiquitin ligase mouse double minute 2 (MDM2), a key regulator of EMT. Lastly, the regulation of KLF5 in the biological behaviors of HLECs via MDM2 was analyzed. We found a significant increase of KLF5 in the DC lens anterior capsular, diabetic rat lens, and high glucose (HG)-stimulated HLECs. Knockdown of KLF5 inhibited oxidative stress, inflammation, migration, and EMT of HG-stimulated HLECs. KLF5 silencing impeded MDM2 expression and restricted the activation of MARK1/FAK and NF-κB signaling pathways in HLECs under HG condition. Additionally, KLF5 was found to bind the MDM2 promoter and enhance the transcriptional activity of MDM2. The protective effects by silencing KLF5 on HG-cultured HLECs could be offset by MDM2 overexpression. We demonstrated that knockdown of KLF5 alleviated oxidative stress, migration, and EMT of HG-cultured HLECs by regulating MDM2, suggesting a potential therapeutic strategy for DC.

Aquaporins contribute to vacuoles formation in Nile grass type II diabetic rats.

Regulation of ion and water microcirculation within the lens is tightly controlled through aquaporin channels and connexin junctions. However, cataracts can occur when the lens becomes cloudy. Various factors can induce cataracts, including diabetes which is a well-known cause. The most common phenotype of diabetic cataracts is a cortical and/or posterior subcapsular opacity. In addition to the three main types and two subtypes of cataracts, a vacuole formation is frequently observed; however, their origin remains unclear. In this study, we focused on the aquaporins and connexins involved in diabetes-induced cataracts and vacuoles in Nile grass type II diabetes. The results showed that the expression of aquaporin 0 and aquaporin 5 increased, and that of connexin 43 decreased in diabetic rat lenses. Additionally, aquaporin 0 and 5 were strongly localized in peripheral of vacuoles, suggesting that aquaporins are involved in vacuoles formation. Transillumination photography revealed large vacuoles at the tip of the Y-suture in the anterior capsule of the diabetic lens, and several small vacuoles were observed in the posterior capsule. Within the vacuoles, cytoplasmic degradation and aggregation of fibrous material were observed. Our findings suggest that aquaporins are potential candidate proteins for preventing vacuole formation.

Inhibitory effect of Nifedipine on aldose reductase delays cataract progression.

Aldose reductase (ALR2) is a rate-limiting component of the polyol pathway, which is essential for the NADPH-mediated conversion from glucose to sorbitol. ALR2 dysregulation has been linked to α-crystallin aggregation, increased oxidative stress, and calcium inflow, all of which contribute to a diabetic cataract. Given its crucial role in occular pathologies, ALR2 has emerged as a promising target to treat oxidative stress and hyperglycaemic condition which form the underlying cause of diabetic cataracts. However, several of them had issues with sensitivity and specificity to ALR2, despite being screened as effective ALR2 inhibitors from a wide range of structurally varied molecules. The current study investigates the inhibitory potential of Nifedipine, an analog of the dihydro nicotinamide class of compounds against ALR2 activity. The enzyme inhibition studies were supported by in vitro biomolecular interactions, molecular modeling approaches, and in vivo validation in diabetic rat models. Nifedipine demonstrated appreciable inhibitory potential with the purified recombinant hAR (human aldose reductase; with an IC50 value of 2.5µM), which was further supported by Nifedipine-hAR binding affinity (Kd = 2.91 ± 1.87 × 10-4M) by ITC and fluorescence quenching assays. In the in vivo models of STZ-induced diabetic rats, Nifedipine delayed the onset progression of cataracts by preserving the antioxidant enzyme activity (SOD, CAT, and GPX GSH, TBARS, and protein carbonyls) and was shown to retain the α-crystallin chaperone activity by reducing the calcium levels in the diabetic rat lens. In conclusion, our results demonstrate effective inhibition of ALR2 by Nifedipine, resulting in amelioration of diabetic cataract conditions by lowering oxidative and osmotic stress while retaining the chaperone activity of α-crystallins. The present study could be envisaged to improve the eye condition in older adults upon Nifedipine treatment.

TFEB-Mediated Lysosomal Restoration Alleviates High Glucose-Induced Cataracts Via Attenuating Oxidative Stress.

PurposeDiabetic cataract (DC) is a visual disorder arising from diabetes mellitus (DM). Autophagy, a prosurvival intracellular process through lysosomal fusion and degradation, has been implicated in multiple diabetic complications. Herein, we performed in vivo and in vitro assays to explore the specific roles of the autophagy-lysosome pathway in DC.MethodsStreptozotocin-induced DM and incubation in high glucose (HG) led to rat lens opacification. Protein Simple Wes, Western blot, and immunoassay were utilized to investigate autophagic changes in lens epithelial cells (LECs) and lens fiber cells (LFCs). RNA-sequencing (RNA-seq) was performed to explore genetic changes in the lenses of diabetic rats. Moreover, autophagy-lysosomal functions were examined using lysotracker, Western blot, and immunofluorescence analyses in HG-cultured primary rabbit LECs.ResultsFirst, DM and HG culture led to fibrotic LECs, swelling LFCs, and eventually cataracts. Further analysis showed aberrant autophagic degradation in LECs and LFCs during cataract formation. RNA-seq data revealed that the differentially expressed genes (DEGs) were enriched in the lysosome pathway. In primary LECs, HG treatment resulted in decreased transcription factor EB (TFEB) and cathepsin B (CTSB) activity, and increased lysosomal size and pH values. Moreover, TFEB-mediated dysfunctional lysosomes resulted from excessive oxidative stress in LECs under HG conditions. Furthermore, TFEB activation by curcumin analog C1 alleviated HG-induced cataracts through enhancing lysosome biogenesis and activating protective autophagy, thereby attenuating HG-mediated oxidative damage.ConclusionsIn summary, we first identified that ROS-TFEB-dependent lysosomal dysfunction contributed to autophagy blockage in HG-induced cataracts. Additionally, TFEB-mediated lysosomal restoration might be a promising therapeutic method for preventing and treating DC through mitigating oxidative stress.

Efficacy of N-Acetylcysteine (NAC) Against Malondialdehyde (MDA) Levels in Diabetic Cataracts: In vivo Study

Background: Diabetes mellitus is a systemic condition that affects various organs, including the eyes. N-acetylcysteine ​​(NAC) functions as an antioxidant because it belongs to a thiol group synthesis glutathione. However, the availability of cysteine ​​in the body is only 15%, so cysteine ​​supplementation can help with oxidative stress in diabetic cataracts. That it will prevent the reaction of lipid peroxidase and the formation of PUFA in the lens membrane, which causes damage to lens cells and is characterized by an increase in malondialdehyde. This study aims to determine the comparison of malondialdehyde levels in the lenses of diabetic cataract rats given or without topical NAC.
 Methods: 36 rats were divided into the control group (received streptozotocin) and treatment group (received streptozotocin and topical NAC. Intraperitoneal injection of streptozotocin was given 90 mg/kg BW and performed once a week for 3 weeks. GDP examination was performed the next day after the rats fasted for 16 hours from the vein. In the tail, GDP > 110 mg/dl categorized as diabetes. Topical NAC was given 4 times per day for 3 weeks. At the end of the study, the lens was extracted for the measurement of malondialdehyde.
 Results: The mean MDA levels in the control group were higher (2.90±0.71nmol/ml) than in the treatment group (2.33±0.38nmol/ml), p<0.05.
 Conclusion: NAC was effective in reducing oxidative stress levels in diabetic cataract lenses by lowering MDA levels better than the group that did not receive MDA in vivo.

The effects of vanadyl sulfate on glutathione, lipid peroxidation and nonenzymatic glycosylation levels in various tissues in experimental diabetes

Background and Aims: Diabetes mellitus is characterized by hyperglycemia which over time leads to serious damage of several body systems. Vanadium ions and their complexes have been demonstrated to have various insulin-mimetic and antidiabetic effects. The object of the present work was to investigate the effect of vanadyl sulfate (VS) on serum total lipid and protein parameters, glutathione, lipid peroxidation and nonenzymatic glycosylation levels in cardiac, lens, lung and skeletal muscle tissues of STZ diabetic rats. Methods: Randomly selected 6.0 - 6.5 month old Swiss Albino rats were separated into two diabetic and two control groups. A single intraperitoneal injection of 65 mg/kg streptozotocin (STZ) in 0.01 M citrate buffer (pH 4.5) was used to induce diabetes. 100 mg/kg VS was administered daily to one of the controls and one of the diabetic groups. On the 60th day of the experiment, serum total lipid and total protein levels were determined. Results: Tissue samples were taken and used for determination of glutathione (GSH), lipid peroxidation (LPO) and nonenzymatic glycosylation (GSH) and protein levels. Conclusion: According to the results, treatment with VS reversed the effects of diabetes by exerting antioxidant properties and preventing damage caused by diabetes on various tissues along with some serum parameters.

Prevention of Diabetic Complications by Walnut Leaf Extract via Changing Aldose Reductase Activity: An Experiment in Diabetic Rat Tissue.

Background Increased activity of aldose reductase (AR) is one of the mechanisms involved in the development of diabetic complications. Inhibiting AR can be a target to prevent diabetes complications. This study is aimed at evaluating the effect of cyclohexane (CH) and ethanol extracts (ET) of walnut leaves on AR activity in the lens and testis of diabetic rats. Methods Fifty-six male rats classified into seven groups as control and treatment groups and treated for 30 days. The treatment groups were treated with different concentrations of ET and CH. The diabetic control (DC) group was exposed to streptozotocin. AR activity was measured in the lens and testis. The expression of AR in the testis was evaluated by the immunohistochemistry method. Results Both extracts significantly reduced the AR activity (ng/mg of tissue protein) in the testis (0.034 ± 0.004, 0.038 ± 0.010, and 0.040 ± 0.007 in the treatment groups vs. 0.075 ± 0.007 in the DC group) and lens (1.66 ± 0.09, 2.70 ± 0.47, and 1.77 ± 0.20 in the treatment groups vs. 6.29 ± 0.48 in the DC group) of the treatment group compared to those of the DC group (P < 0.05). AR expression in the testes of the treatment groups was decreased compared with that of the DC group (P < 0.0001). Conclusion Walnut leaf extracts can reduce the activity and localization of AR in the testes and its activity in the lens of diabetic rats.

Effect of Berberine on Glycation, Aldose Reductase Activity, and Oxidative Stress in the Lenses of Streptozotocin-Induced Diabetic Rats In Vivo-A Preliminary Study.

Diabetes mellitus affects the eye lens, leading to cataract formation by glycation, osmotic stress, and oxidative stress. Berberine, an isoquinoline alkaloid, is a natural compound that has been reported to counteract all these pathological processes in various tissues and organs. The goal of this study was to evaluate whether berberine administered at a dose of 50 mg/kg by oral gavage for 28 days to rats with streptozotocin-induced diabetes reveals such effects on the biochemical parameters in the lenses. For this purpose, the following lenticular parameters were studied: concentrations of soluble protein, non-protein sulfhydryl groups (NPSH), advanced oxidation protein products (AOPP), advanced glycation end-products (AGEs), thiobarbituric acid reactive substances (TBARS), and activities of aldose reductase (AR), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Diabetes induced unfavorable changes in the majority of the examined parameters. The administration of berberine resulted in an increased soluble protein level, decreased activity of AR, and lowered AOPP and AGEs levels. The results suggest that berberine administered orally positively affects the lenses of diabetic rats, and should be further examined with regard to its anticataract potential.

Antidiabetic and aldose reductase inhibitory potentials ofLand caltropsaqueous extract in streptozotocin-nicotinamide induced diabetic rats

Introduction:Diabetic retinopathy is a late stage complication in diabetic patients and one which dramatically affects quality of life. Persistent hyperglycemia results in sorbitol accumulation due to increased activity of aldose reductase (AR), which leads to changes in membrane permeability and leakage of glutathione (GSH) from the lens which in turn results in the development of cataract and retinopathy. Hence, the present study was designed to assess the effect ofTribulus terrestrison AR activity and GSH level in diabetic rat lens, random blood glucose, hemoglobin A1c (HbA1c) and insulin.Methods:Diabetes mellitus was induced by intra-peritoneal (i.p) injection of streptozotocinnicotinamide (STZ-NA). Animals were divided into 5 groups including normal controls (NC) treated with saline, untreated diabetic controls (DC),T. terrestris(150 and 300 mg/kg) and glibenclamide (500 µg/kg) treated diabetic rats. After 16 weeks of treatment, the rats were sacrificed, the lens was removed through posterior approach and homogenate was prepared for AR activity estimation. The lens tissue homogenate was prepared in normal saline for the estimation of GSH. Blood glucose was estimated by glucometer, HbA1c by nephelometry and insulin by ELISA kit.Results:AR activity was significantly reduced (P&lt;0.004) inT. terrestris(both doses) treated groups compared to untreated diabetic controls. GSH levels were found significantly higher (P&lt;0.005) in treated groups than the ones in diabetic controls. Glucose, HbA1c and insulin were significantly improved (P&lt;0.004) in plant extract treated groups when compared to untreated diabetic rats.Conclusion:Tribulus terrestrisaqueous extract may be useful as AR inhibitor. It also has antioxidant and antidiabetic activities and thereby might be capable of controlling the hyperglycemia induced tissue damage.

Chrysin Reduces Oxidative Stress but Does Not Affect Polyol Pathway in the Lenses of Type 1 Diabetic Rats.

Prolonged hyperglycemia is one of the main causes of reactive oxygen species and free radicals generation in diabetes which may affect various organs, including the eye. Oxidative damage to proteins and lipids in the eye lens could lead to cataract formation. To cope with oxidative stress, the endogenous antioxidative system may be supported by the supplementation of exogenous antioxidants. The aim of this study was to evaluate the effect of chrysin, a natural flavonoid, on oxidative stress and polyol pathway-related markers in the lenses of streptozotocin-induced type 1 male diabetic rats. Chrysin at doses of 50 and 100 mg/kg was administered by gavage for 28 days. This treatment resulted in a decrease in antioxidative enzymes activity and oxidative stress index. Moreover, chrysin administration elevated the reduced glutathione level in the lenses. A decrease in the markers linked to oxidative damage to proteins and lipids in the lenses was noted, especially after treatment with 50 mg/kg of chrysin. Neither of the chrysin doses affected glycemia-related markers in the serum or altered parameters related to the polyol pathway and advanced glycation end-products level in the lenses of diabetic rats. Upon obtaining results, it can be concluded that chrysin reveals antioxidative activity in the lenses but shows no antihyperglycemic or antiglycation properties.

Efficacy of melatonin in restoring the antioxidant status in the lens of diabetic rats induced by streptozotocin.

Melatonin is a well-known free radical scavenger. The present study aimed to investigate the effects of melatonin treatment on the antioxidant status in the lenticular tissue of streptozotocin (STZ)-induced diabetic rats. Thirty-four male rats were randomly divided into four groups as follows: healthy control rats (group 1, n = 10); diabetic control rats (group 2, n = 10); melatonin-treated (5mg/kg·day) diabetic rats (group 3, n = 10) and melatonin-treated (5mg/kg·day) healthy rats (group 4, n = 4). Diabetes was induced by injection of streptozotocin (50mg/kg, ip). Following 8-weeks of melatonin treatment, all rats were killed and the blood plasma and their lenses were stored at -70°C for antioxidant enzyme activities assay and biochemical determination. The plasma glucose and lens malondialdehyde (MDA) increased significantly in the rats of group 2 as compared to the group 1. Also, a significant decrease in the levels of catalase (CAT) and glutathione reductase (GR) activities in the lenses and plasma reduced glutathione (GSH) was found. However, the levels of lenticular MDA (not significant) and the plasma glucose significantly decreased in the rats of group 3 compared to the group 2. Besides, the levels of CAT, GR in the rats lens and plasma GSH increased significantly. Diabetes mellitus induced hyperglycemia and oxidative stress, whereas melatonin decreased the blood glucose levels and lipid peroxidation and increased the activities of antioxidant enzymes in diabetic rat lenses.

Involvement of Oxidation and Glycation in Protein Modification in Diabetic Rat Lens

Involvement of Oxidation and Glycation in Protein Modification in Diabetic Rat Lens

Trapa bispinosa Roxb. and lutein ameliorate cataract in type 1 diabetic rats.

Trapa bispinosa Roxb. is an annual aquatic grass of the citrus family. Although its hot water extract displays antioxidative activity in vitro, little is known about its biological effectiveness. In the present study, we evaluated the extract’s inhibitory effect on diabetic cataractogenesis and formation of advanced glycation end-product. Lutein, which is beneficial for eye diseases, was administered concurrently. For short-term administration, Trapa bispinosa Roxb. hot water extract and/or lutein were administered to type 1 diabetic rats. Nɛ-(carboxymethyl)lysine and Nɛ-(carboxyethyl)lysine were quantified in serum using mass spectrometry. The long-term administration study was similar to the short-term, except that the dosages were lower. In the short-term study, co-administration of the extract and lutein inhibited Nɛ-(carboxymethyl)lysine and Nɛ-(carboxyethyl)lysine in serum. However, in the long-term study, only lutein inhibited Nɛ-(carboxymethyl)lysine and Nɛ-(carboxyethyl)lysine in serum. These results suggest that lutein exerts its long-term effect regardless of the concentration administered, while the extract exerts its effect when its concentration is increased. Relative to the consumption of the control diet, oral intake of the combination of the extract and lutein significantly inhibited the progression of cataractogenesis in the lens of diabetic rats, even at low doses, and the combination was more effective than individual treatments.

Glucoselysine is derived from fructose and accumulates in the eye lens of diabetic rats

Prolonged hyperglycemia generates advanced glycation end-products (AGEs), which are believed to be involved in the pathogenesis of diabetic complications. In the present study, we developed a polyclonal antibody against fructose-modified proteins (Fru-P antibody) and identified its epitope as glucoselysine (GL) by NMR and LC-electrospray ionization (ESI)- quadrupole TOF (QTOF) analyses and evaluated its potential role in diabetes sequelae. Although the molecular weight of GL was identical to that of fructoselysine (FL), GL was distinguishable from FL because GL was resistant to acid hydrolysis, which converted all of the FLs to furosine. We also detected GL in vitro when reduced BSA was incubated with fructose for 1 day. However, when we incubated reduced BSA with glucose, galactose, or mannose for 14 days, we did not detect GL, suggesting that GL is dominantly generated from fructose. LC-ESI-MS/MS experiments with synthesized [13C6]GL indicated that the GL levels in the rat eye lens time-dependently increase after streptozotocin-induced diabetes. We observed a 31.3-fold increase in GL 8 weeks after the induction compared with nondiabetic rats, and Nϵ-(carboxymethyl)lysine and furosine increased by 1.7- and 21.5-fold, respectively, under the same condition. In contrast, sorbitol in the lens levelled off at 2 weeks after diabetes induction. We conclude that GL may be a useful biological marker to monitor and elucidate the mechanism of protein degeneration during progression of diabetes.

Effect of caffeine on biomarkers of oxidative stress in lenses of rats with streptozotocin-induced diabetes.

IntroductionOne of the major causes of cataract in diabetes is oxidative stress induced by reactive oxygen species (ROS). Nowadays, new substances with antioxidative properties that may prevent cataract development are needed. One such substance is caffeine – an alkaloid with well-documented antioxidative activity.Material and methodsThe study was conducted on lenses obtained from female rats, divided into 3 groups: control rats; diabetic rats; diabetic rats treated with caffeine at a dose of 20 mg/kg p.o. Type 1 diabetes was induced by streptozotocin (60 mg/kg i.p.). After 4 weeks of caffeine administration, the rats were sacrificed, and the lenses were collected, weighed and homogenized in PBS. The homogenate was used for analysis of protein content, glutathione (GSH) concentration, advanced oxidation protein product (AOPP) concentration, malondialdehyde (MDA) concentration and the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx).ResultsThe SOD, CAT and GPx activities were found to be higher in the lenses of diabetic rats. There were also increased MDA and AOPP concentrations as well as decreased GSH concentration. The administration of caffeine resulted in decreased activity of SOD, CAT and GPx. The treatment with caffeine also caused an increase of GSH concentration and a decrease of MDA and AOPP concentrations.ConclusionsThe results of the present study may be of relevance in determining the effect of caffeine on the processes induced by ROS in vivo. Further, they can be an indication for clinical observations aiming at the assessment of both preventive and therapeutic effects of caffeine in cataract.

Effect of Resveratrol, a Dietary-Derived Polyphenol, on the Oxidative Stress and Polyol Pathway in the Lens of Rats with Streptozotocin-Induced Diabetes.

Resveratrol is found in grapes, apples, blueberries, mulberries, peanuts, pistachios, plums and red wine. Resveratrol has been shown to possess antioxidative activity and a variety of preventive effects in models of many diseases. The aim of the study was to investigate if this substance may counteract the oxidative stress and polyol pathway in the lens of diabetic rats. The study was conducted on the rats with streptozotocin-induced type 1 diabetes. After the administration of resveratrol (10 and 20 mg/kg po for 4 weeks), the oxidative stress markers in the lens were evaluated: activity of superoxide dismutase, catalase and glutathione peroxidase, as well as levels of total and soluble protein, level of glutathione, vitamin C, calcium, sulfhydryl group, advanced oxidation protein products, malonyldialdehyde, Total Oxidant Status and Total Antioxidant Reactivity. The obtained results indicate that the administration of resveratrol to the diabetic rats shows antioxidative properties. It is not a result of antiglycaemic activity but resveratrol probably directly affects the antioxidative system. Resveratrol did not affect the polyol pathway in the lens of diabetic rats. Our results may indirectly indicate benefits of consumption of foods as well as dietary supplements containing resveratrol in diminishing oxidative stress in lenses of individuals suffering from diabetes mellitus.

Anti-cataract Effect of Resveratrol in High-Glucose-Treated Streptozotocin-Induced Diabetic Rats.

Resveratrol, which is a polyphenol found in grapes, peanuts, and other plants, has health benefits for various chronic diseases. The aim of the present study was to examine the effect of resveratrol on cataract formation in diabetic rats. Male Wistar rats (7-week-old) were treated with streptozotocin, and the streptozotocin-treated animals were administered 5% D-glucose in drinking water to promote the formation of cataracts by inducing severe hyperglycemia. Resveratrol supplementation (10 or 30 mg/kg/d) in drinking water was initiated immediately after induction of diabetes was confirmed. The full lens images of the horizontal plane were captured with the digital camera system which we developed. Cataract formation was assessed by an observer-based scoring method and by quantitative analysis of digital images of the lens. Cataracts at the peripheral region of the lens were detected 2 weeks after induction of hyperglycemia and progressed depending on the length of the diabetic period. The majority of them developed severe cataracts after 9 weeks of hyperglycemia. Resveratrol did not prevent the appearance of diabetic cataracts but significantly delayed the progression of cataracts compared with controls. The contents of sorbitol and protein carbonyls in lenses of diabetic rats were higher than those of control rats. Resveratrol suppressed the increase in protein carbonyls, but not of sorbitol, in diabetic lenses. These results suggest that resveratrol delays the progression of diabetic cataracts partially through attenuation of oxidative damage to lens proteins. Resveratrol may be beneficial in preventing the progression of diabetic cataracts.

Zinc Supplementation Ameliorates Diabetic Cataract Through Modulation of Crystallin Proteins and Polyol Pathway in Experimental Rats.

Non-enzymatic glycation of lens proteins and elevated polyol pathway in the eye lens have been the characteristic features of a diabetic condition. We have previously reported the benefits of zinc supplementation in reducing hyperglycemia and associated metabolic abnormalities and oxidative stress in diabetic rats. The current study explored whether zinc supplementation protects against cataractogenesis through modulation of glycation of lens proteins, elevated polyol pathway, oxidative stress, and proportion of different heat shock proteins in the eye lens of diabetic rats. Streptozotocin-induced diabetic rats were fed with a zinc-enriched diet (5 and 10 times of normal) for 6weeks. Supplemental zinc alleviated the progression and maturation of diabetes-induced cataract. Zinc was also effective in preventing the reduced content of total and imbalanced proportion of soluble proteins in the lens. Supplemental zinc also alleviated cross-linked glycation and concomitant expression of the receptor of glycated products and oxidative stress indicators in the eye lens. Zinc supplementation further induced the concentration of heat shock protein in the eye lens of diabetic rats, specifically α-crystallin. Zinc supplementation counteracted the elevated activity and expression of polyol pathway enzymes and molecules in the lens. The results of this animal study endorsed the advantage of zinc supplementation in exerting the antiglycating influence and downregulating polyol pathway enzymes to defer cataractogenesis in diabetic rats.

Evaluation of the effects of saffron aqueous extract on oxidative stress in the lens of streptozotocin-induced diabetic rats

Background: Multiple-organ failure is the main cause of disability and death in diabetes mellitus. Imbalance in oxidative status is responsible for major diabetic complications and multiple-organ failure including blindness. Recently, plants with potential antioxidant properties have been used to manage hyperglycemia in diabetes. This study was undertaken to evaluate the beneficial effects of saffron aqueous extract (SAE) administration in streptozotocin (STZ)-induced diabetic rats by evaluation of oxidative stress parameters in the eye lens. Methods: Thirty-two adult rats were randomly divided into four groups: normal control (I), saffron control (II), diabetic control (III), and saffron treated (IV). Diabetes was induced in animals by a single intraperitoneal (i.p.) injection of STZ (60 mg/kg body weight). Three days after STZ administration, diabetes was confirmed by measuring fasting blood glucose. At this time, groups II and IV were treated with SAE (200 mg/kg body weight) for a total of 5 doses, and then weekly from the 7th day after STZ injection. At the end of study, fasting blood glucose levels, activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as malondialdehyde (MDA) content were determined in the lens tissues. Results: In addition to the effects of SAE on blood glucose, SAE was effective on the enzymatic antioxidant defense system. The level of antioxidant enzymes (SOD, CAT, and GPx) decreased while there was an increase in the levels of MDA in the lens tissues of diabetic control rats, as compared to normal control rats. SAE could be modulating the changes in these parameters that are induced by diabetes. Conclusion: The results of the present study demonstrate that SAE is able to control blood glucose and thus may be useful in delaying the complicated effects of diabetes, such as clouding of the eyes’ lens due to the antioxidant effect of SAE.

Effects of calcium dobesilate on Nrf2, Keap1 and HO-1 in the lenses of D-galactose-induced cataracts in rats.

This study investigated the effects of calcium dobesilate on Nrf2, Keap1 and HO-1 in the lenses of D-galactose-induced cataracts in rats. Thirty Sprague-Dawley rats were randomly divided into three groups: a blank control group, a model control group and a model administration group. A normal diet was given to the rats in the blank control group and the rats with D-galactose-induced cataracts of the model control group. Calcium dobesilate was also given to the rats with D-galactose-induced cataracts of the model administration group. A slit lamp microscope was used to check the degree of lens opacity. RT-PCR and western blot analysis were used to detect the mRNA and protein expression of Nrf2, Keap1 and HO-1 in the lenses of the three groups. There was a significant difference in the degree of lens opacity among the three groups (P<0.05). The model control group was the most turbid of the three groups, followed by the model administration group. Moreover, the mRNA and protein expression of Nrf2, Keap1 and HO-1 in the lenses of the three groups were also significantly different (P<0.05). The mRNA levels of Nrf2 and HO-1 were the highest in the model control group, followed by the model administration group, and were the lowest in the blank control group. However, the mRNA expression level of Keap1 among the three groups had an opposite trend. In conclusion, calcium dobesilate can effectively increase the levels of Nrf2 and HO-1 in the lenses of diabetic cataract rats and inhibit the level of Keap1. Therefore, the therapeutic effect of calcium dobesilate against cataracts is related to the improvement of the Nrf2-Keap1 signaling pathway.