scholarly journals Vitamin K1 prevents diabetic cataract by inhibiting lens aldose reductase 2 (ALR2) activity

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
R. Thiagarajan ◽  
M. K. N. Sai Varsha ◽  
V. Srinivasan ◽  
R. Ravichandran ◽  
K. Saraboji
Keyword(s):  
Aldose Reductase ◽  
Potent Inhibitor ◽  
Reductase Activity ◽  
Protein Docking ◽  
Diabetic Rats ◽  
Exact Nature ◽  
Vitamin K1 ◽  
Diabetic Cataract ◽  
Single Intraperitoneal Injection ◽  
Pure Protein

Abstract This study investigated the potential of vitamin K1 as a novel lens aldose reductase inhibitor in a streptozotocin-induced diabetic cataract model. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, activation of lens aldose reductase 2 (ALR2) and accumulation of sorbitol in eye lens which could have contributed to diabetic cataract formation. However, when diabetic rats were treated with vitamin K1 (5 mg/kg, sc, twice a week) it resulted in lowering of blood glucose and inhibition of lens aldose reductase activity because of which there was a corresponding decrease in lens sorbitol accumulation. These results suggest that vitamin K1 is a potent inhibitor of lens aldose reductase enzyme and we made an attempt to understand the nature of this inhibition using crude lens homogenate as well as recombinant human aldose reductase enzyme. Our results from protein docking and spectrofluorimetric analyses clearly show that vitamin K1 is a potent inhibitor of ALR2 and this inhibition is primarily mediated by the blockage of DL-glyceraldehyde binding to ALR2. At the same time docking also suggests that vitamin K1 overlaps at the NADPH binding site of ALR2, which probably shows that vitamin K1 could possibly bind both these sites in the enzyme. Another deduction that we can derive from the experiments performed with pure protein is that ALR2 has three levels of affinity, first for NADPH, second for vitamin K1 and third for the substrate DL-glyceraldehyde. This was evident based on the dose-dependency experiments performed with both NADPH and DL-glyceraldehyde. Overall, our study shows the potential of vitamin K1 as an ALR2 inhibitor which primarily blocks enzyme activity by inhibiting substrate interaction of the enzyme. Further structural studies are needed to fully comprehend the exact nature of binding and inhibition of ALR2 by vitamin K1 that could open up possibilities of its therapeutic application.

scholarly journals Anticataractogenesis and Antiretinopathy Effects of the Novel Protective Agent Containing the Combined Extract of Mango and Vietnamese Coriander in STZ-Diabetic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Paphaphat Thiraphatthanavong ◽  
Wipawee Thukham-mee ◽  
Supaporn Muchimapura ◽  
Panakaporn Wannanond ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Aldose Reductase ◽  
Diabetic Rats ◽  
Potential Candidate ◽  
Protective Agent ◽  
The Novel ◽  
Diabetic Cataract ◽  
Oxidative Stress Status ◽  
Mango Seed

The novel protectant against diabetic cataract and diabetic retinopathy is currently required due to the increased prevalence and therapeutic limitation. Based on the advantage of polyphenol on diabetic eye complications, we hypothesized that the combined extract of mango seed Vietnamese coriander (MPO), a polyphenol-rich substance, should possess anticataractogenesis and antiretinopathy in streptozotocin- (STZ-) diabetic rats. MPO at doses of 2, 10, and 50 mg/kg·BW were orally given to STZ-diabetic rats for 10 weeks. Lens opacity was evaluated every week throughout a study period whereas the evaluation of cataract severity and histological changes of both rat lens epithelium and retina together with the biochemical assays of oxidative stress status, aldose reductase, p38MAPK, ERK1/2, and VEGF were performed at the end of experiment. Our data showed that MPO improved cataract and retinopathy in STZ-diabetic rats. The improved oxidative stress status and the decreased p38MAPK, ERK1/2, and VEGF were also observed. Therefore, anticataractogenesis and antiretinopathy of MPO might occur partly via the decreased oxidative stress status and the suppression of aldose reductase, p38MAPK, ERK1/2, and VEGF. This study points out that MPO is the potential candidate protectant against diabetic cataract and diabetic retinopathy. However, the exploration for possible active ingredient (S) still requires further researches.

Design and development of novel thiazole-sulfonamide derivatives as a protective agent against diabetic cataract in Wistar rats via inhibition of aldose reductase

2021 ◽  
Vol 27 (1) ◽  
pp. 63-70
Author(s):  
Liang Yin ◽  
Mingxue Zhang ◽  
Tiangeng He
Keyword(s):  
Body Weight ◽  
Western Blot ◽  
Aldose Reductase ◽  
Wistar Rats ◽  
Potent Inhibitor ◽  
Insulin Level ◽  
Protective Agent ◽  
Diabetic Cataract ◽  
Reductase Inhibitors ◽  
Glucose Output

Abstract In recent years, ALR2 (aldose reductase) inhibitors have attracted attention for their effective ability to reduce the progression of diabetes-associated cataracts. Therefore, in the present article, we intended to develop novel thiazole-sulfonamide hybrids as a potent inhibitor of ALR2. These molecules significantly inhibited the ALR2 level in the rat lenses homogenate, where the most potent compound 7b showed activity comparable to sorbinil as standard. In Wistar rats, compound 7b improved the insulin level and body weight of the experimental animal together with a reduction in the glucose output. Compound 7b showed a significant reduction in the expression of ALR2 in rat lenses in western blot analysis.

Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress

2008 ◽  
Vol 294 (5) ◽  
pp. H2305-H2312 ◽  
Author(s):  
Yu-Jung Chen ◽  
Jing Li ◽  
John Quilley
Keyword(s):  
Oxidative Stress ◽  
Aldose Reductase ◽  
Reductase Activity ◽  
Rat Kidney ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Glucose Levels ◽  
Nitric Oxide Formation ◽  
Streptozotocin Induced Diabetes ◽  
And Control

We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated perfused kidney of diabetic rats is greatly reduced compared with age-matched control rats. The present studies were undertaken to examine potential mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3–4 wk duration. A role for oxidative stress was excluded, inasmuch as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric oxide formation with nitro-l-arginine methyl ester or aldose reductase with zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney. Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the expression/activity of which is increased in diabetes, we included indomethacin in the perfusate of the isolated kidney to inhibit COX but found no effect on 20-HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that would restore release of 20-HETE from the diabetic rat kidney. However, fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk to reverse the hyperglycemia and maintain blood glucose levels at <200 mg/dl reversed the renal deficit in 20-HETE. We conclude that oxidative stress, increased aldose reductase activity, or increased COX activity does not contribute to the renal deficit of 20-HETE in diabetes, which may be directly related to insulin deficiency.

Increased renal aldose reductase activity, immunoreactivity, and mRNA in streptozocin-induced diabetic rats

Diabetes ◽  
1989 ◽  
Vol 38 (8) ◽  
pp. 1067-1071 ◽  
Author(s):  
A. Ghahary ◽  
J. M. Luo ◽  
Y. W. Gong ◽  
S. Chakrabarti ◽  
A. A. Sima ◽  
...  
Keyword(s):  
Aldose Reductase ◽  
Reductase Activity ◽  
Diabetic Rats

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

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zahra Abbasi ◽  
Gholamali Jelodar ◽  
Bita Geramizadeh
Keyword(s):  
Aldose Reductase ◽  
Diabetic Complications ◽  
Reductase Activity ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Male Rats ◽  
Diabetic Rat ◽  
Leaf Extracts ◽  
Treatment Groups ◽  
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.

scholarly journals Increased Renal Aldose Reductase Activity, Immunoreactivity, and mRNA in Streptozocin-Induced Diabetic Rats

Diabetes ◽  
1989 ◽  
Vol 38 (8) ◽  
pp. 1067-1071 ◽  
Author(s):  
A. Ghahary ◽  
J. Luo ◽  
Y. Gong ◽  
S. Chakrabarti ◽  
A. A. F. Simaand ◽  
...  
Keyword(s):  
Aldose Reductase ◽  
Reductase Activity ◽  
Diabetic Rats

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

2020 ◽  
Vol 21 (12) ◽  
pp. 4278
Author(s):  
Maria Zych ◽  
Weronika Wojnar ◽  
Magdalena Kielanowska ◽  
Joanna Folwarczna ◽  
Ilona Kaczmarczyk-Sedlak
Keyword(s):  
Oxidative Stress ◽  
Aldose Reductase ◽  
Soluble Protein ◽  
Reductase Activity ◽  
Thiobarbituric Acid ◽  
Isoquinoline Alkaloid ◽  
Diabetic Rats ◽  
Protein Sulfhydryl Groups ◽  
And Oxidative Stress

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.

scholarly journals Litsea japonicaExtract Inhibits Aldose Reductase Activity and Hyperglycemia-Induced Lenticular Sorbitol Accumulation in db/db Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Junghyun Kim ◽  
Chan-Sik Kim ◽  
Eunjin Sohn ◽  
Yun Mi Lee ◽  
Kyuhyung Jo ◽  
...  
Keyword(s):  
Aldose Reductase ◽  
Reductase Activity ◽  
Polyol Pathway ◽  
Protective Mechanism ◽  
Diabetic Cataract ◽  
Fiber Cells ◽  
Lens Opacification ◽  
Treatment Of Diabetes ◽  
Rate Limiting

Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway. AR-dependent synthesis of excess polyols leads to lens opacification in diabetic cataract. The purpose of this study is to investigate the protective effect ofLitsea japonicaextract (LJE) on diabetes-induced lens opacification and its protective mechanism in db/db mice. Seven-week-old male db/db mice were treated with LJE (100 and 250 mg/kg body weight) once a day orally for 12 weeks. LJE dose dependently inhibited rat lens aldose reductase activityin vitro(IC50= 13.53 ± 0.74 µg/mL). In db/db mice, lens was slightly opacified, and lens fiber cells were swollen and ruptured. In addition, lenticular sorbitol accumulation was increased in db/db mice. However, the administration of LJE inhibited these lenticular sorbitol accumulation and lens architectural changes in db/db mice. Our results suggest that LJE might be beneficial for the treatment of diabetes-induced lens opacification. The ability of LJE to suppress lenticular sorbitol accumulation may be mediated by the inhibition of AR activity.

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