scholarly journals Water-soluble C60 fullerene ameliorates astroglial reactivity and TNFa production in retina of diabetic rats

2019 ◽  
Vol 10 (4) ◽  
pp. 513-519 ◽  
Author(s):  
V. S. Nedzvetsky ◽  
E. V. Sukharenko ◽  
G. Baydas ◽  
G. V. Andrievsky
Keyword(s):  
Critical Role ◽  
Diabetic Rats ◽  
Fullerene C60 ◽  
Water Soluble ◽  
C60 Fullerene ◽  
Diabetic Rat ◽  
Retinal Cells ◽  
Diabetes Model ◽  
Anti Inflammatory ◽  
Glial Reactivity

The complications of both first and second types of diabetes mellitus patients are important cause of decline in quality of life and mortality worldwide. Diabetic retinopathy (DR) is a widespread complication that affects almost 60% of patients with prolonged (at least 10–15 years) diabetes. The critical role of glial cells has been shown in retinopathy initiation in the last decades. Furthermore, glial reactivity and inflammation could be key players in early pathogenesis of DR. Despite the large amount of research data, the approaches of effective DR therapy remain unclear. The progress of DR is accompanied by pro-inflammatory and pro-oxidative changes in retinal cells including astrocytes and Muller cells. Glial reactivity is a key pathogenetic factor of various disorders in neural tissue. Fullerene C60 nanoparticles were confirmed for both antioxidant and anti-inflammatory capability. In the presented study glioprotective efficacy of water-soluble hydrated fullerene C60 (C60HyFn) was tested in a STZ-diabetes model during 12 weeks. Exposure of the STZ-diabetic rat group to C60HyFn ameliorated the astrocyte reactivity which was determined via S100β and PARP1 overexpression. Moreover, C60HyFn induced the decrease of TNFα production in the retina of STZ-diabetic rats. By contrast, the treatment with C60HyFn of the normal control rat group didn’t change the content of all abovementioned markers of astrogliosis and inflammation. Thus, diabetes-induced abnormalities in the retina were suppressed via the anti-oxidant, anti-inflammatory and glioprotective effects of C60HyFn at low doses. The presented results demonstrate that C60HyFn can ensure viability of retinal cells viability through glioprotective effect and could be a new therapeutic nano-strategy of DR treatment.

scholarly journals Nanoparticles C60 fullerene prevent reactive gliosis in retina of aged rats under hyperglycemia

2015 ◽  
Vol 6 (2) ◽  
pp. 113-118
Author(s):  
I. V. Prischepa ◽  
O. G. Prokushenkova ◽  
V. S. Nedzvetsky
Keyword(s):  
Diabetic Retinopathy ◽  
Glial Cells ◽  
Glycosylated Hemoglobin ◽  
Initial Period ◽  
Protective Action ◽  
Diabetic Rats ◽  
Water Soluble ◽  
Reactive Gliosis ◽  
C60 Fullerene ◽  
Diabetic Rat

Reactivation of glial cells, induced by metabolic disorders of glucose utilization and development of oxidative stress in retina under diabetes mellitus, is the key pathogenetic factor of diabetic retinopathy. Nanoparticles of C60 fullerene and some of their water-soluble derivates are known as one of the strongest antioxidants having neuroprotective effect in a number of pathologies and harmful influences. In the present study, for the first time, the effects of nanostructures of hydrated C60 fullerene (C60HyFn) on the expression and polypeptide composition of glial fibrillary acidic protein (GFAP) in retina of rats with streptozotocin (STZ)-induced diabetes have been evaluated. Using immunoblotting, 1.93-fold up-regulation of GFAP in diabetic rat retina as compared with control was shown, as a result of retinal glial cells reactivation induced by hyperglycemia. Increase in GFAP-immunolabeling associated with the reactive gliosis development in retina of diabetic rats was also confirmed by immuno-histochemical method. Consumption of C60HyFn solution (90 nM) as drinking water by diabetic rats for 12 weeks caused 1.51-fold decrease of GFAP level compared to untreated diabetic animals. In addition, C60HyFn caused statistically significant lowering of glycosylated hemoglobin concentration in blood serum of STZ-diabetic rats 1.58-fold. However, nanoparticles C60 did not affect neither insulin nor glucose levels in blood of diabetic rats. In conclusion, results obtained indicate that protective action of hydrated fullerene in the initial period of diabetic retinopathy of aged animals is realized through suppression of excessive activation of GFAP-positive retinal cells. 

Functional changes in adenylyl cyclases and associated decreases in relaxation responses in mesenteric arteries from diabetic rats

2005 ◽  
Vol 289 (5) ◽  
pp. H2234-H2243 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Kentaro Wakabayashi ◽  
Tsuneo Kobayashi ◽  
Katsuo Kamata
Keyword(s):  
Mesenteric Artery ◽  
Diabetic Rats ◽  
Functional Change ◽  
Water Soluble ◽  
Mesenteric Arteries ◽  
Diabetic Rat ◽  
Adenylyl Cyclases ◽  
Camp Production ◽  
Functional Changes ◽  
Rat Mesenteric Artery

To assess the functional change in adenylyl cyclases (AC) associated with the diabetic state, we investigated AC-mediated relaxations and cAMP production in mesenteric arteries from rats with streptozotocin (STZ)-induced diabetes. The relaxations induced by the water-soluble forskolin (FSK) analog NKH477, which is a putative AC5 activator, but not by the β-adrenoceptor agonist isoproterenol (Iso) and the AC activator FSK, were reduced in intact diabetic mesenteric artery. In diabetic rats, however, Iso-, FSK-, and NKH477-induced relaxations were attenuated in the presence of inhibitors of nitric oxide synthase and cyclooxygenase. To exclude the influence of phosphodiesterase (PDE), we also examined the relaxations induced by several AC activators in the presence of 3-isobutyl-1-methylxanthine (IBMX; a PDE inhibitor). Under these conditions, the relaxation induced by Iso was greatly impaired in STZ-diabetic rats. This Iso-induced relaxation was significantly attenuated by pretreatment with SQ-22536, an AC inhibitor, in mesenteric rings from age-matched controls but not in those from STZ-diabetic rats. Under the same conditions, the relaxations induced by FSK or NKH477 were impaired in STZ-diabetic rats. Neither FSK- nor A-23187 (a Ca2+ ionophore)-induced cAMP production was significantly different between diabetics and controls. However, cAMP production induced by Iso or NKH477 was significantly impaired in diabetic mesenteric arteries. Expression of mRNAs and proteins for AC5/6 was lower in diabetic mesenteric arteries than in controls. These results suggest that AC-mediated relaxation is impaired in the STZ-diabetic rat mesenteric artery, perhaps reflecting a reduction in AC5/6 activity.

scholarly journals Expression of Endoplasmic Reticulum Stress-Related Factors in the Retinas of Diabetic Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Shu Yan ◽  
Cui Zheng ◽  
Zhi-qi Chen ◽  
Rong Liu ◽  
Gui-gang Li ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Western Blot ◽  
Er Stress ◽  
Diabetic Rats ◽  
Stress Factors ◽  
Diabetic Rat ◽  
Related Factors ◽  
Diabetes Model ◽  
Polymerase Chain

Recent reports show that ER stress plays an important role in diabetic retinopathy (DR), but ER stress is a complicated process involving a network of signaling pathways and hundreds of factors, What factors involved in DR are not yet understood. We selected 89 ER stress factors from more than 200, A rat diabetes model was established by intraperitoneal injection of streptozotocin (STZ). The expression of 89 ER stress-related factors was found in the retinas of diabetic rats, at both 1- and 3-months after development of diabetes, by quantitative real-time polymerase chain reaction arrays. There were significant changes in expression levels of 13 and 12 ER stress-related factors in the diabetic rat retinas in the first and third month after the development of diabetes, Based on the array results, homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1(HERP), and synoviolin(HRD1) were studied further by immunofluorescence and Western blot. Immunofluorescence and Western blot analyses showed that the expression of HERP was reduced in the retinas of diabetic rats in first and third month. The expression of Hrd1 did not change significantly in the retinas of diabetic rats in the first month but was reduced in the third month.

scholarly journals Chitosan-sodium alginate-fatty acid nanocarrier composite: lutein bioavailability, absorption pharmacokinetics in diabetic rat and protection of retinal cells against H2O2 induced oxidative stress in vitro

2020 ◽  
Author(s):  
Veeresh B Toragall ◽  
Baskarn V
Keyword(s):  
Oxidative Stress ◽  
Sodium Alginate ◽  
Mitochondrial Membrane ◽  
Life Time ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Retinal Cells ◽  
Intracellular Ros ◽  
Pre Treatment

Abstract Aiming to enhance therapeutic efficiency of lutein, lutein loaded chitosan-sodium alginate (CS-SA) based nanocarrier composite (LNCs) were prepared and evaluated for lutein bioavailability and pharmacokinetics in diabetic rats in comparison to micellar lutein (control). Further, cytotoxicity, cellular uptake and protective activity against H2O2 induced oxidative stress in ARPE-19 cells were studied. Results revealed that LNCs displayed maximal lutein AUC in plasma, liver and eye respectively in normal (3.1, 2.7 and 5.2 folds) and diabetic (7.3, 3.4 and 2.8 folds) rats. Lutein from LNCs exhibited a higher half-life time, mean residence time and slow clearance from the plasma, indicating prolonged circulation compared to control. In ARPE-19 cells, pre-treatment with LNCs (10 µM) have significantly attenuated H2O2 induced cell death, intracellular ROS and mitochondrial membrane potential compared to control. In conclusion, LNCs improve the lutein bioavailability in conditions like diabetes, diabetic retinopathy and cataract to curtail oxidative stress in retinal cells.

Effects of β-glucan from Aureobasidium pullulans in a Streptozotocininduced Rat Diabetes Model

2020 ◽  
Vol 16 (7) ◽  
pp. 1052-1063
Author(s):  
Jae-Hak Sohn ◽  
Joo Wan Kim ◽  
Jong-Min Lim ◽  
Go-Woon Jung ◽  
Sae Kwang Ku ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Diabetic Complications ◽  
Aureobasidium Pullulans ◽  
Diabetic Rats ◽  
Female Rats ◽  
Diabetic Rat ◽  
Glucose Levels ◽  
Diabetes Model ◽  
Serum Aspartate Aminotransferase

Background: The alleviating effects of diabetic nephropathy and hepatopathy of β-glucan were evaluated in this study. Objective: The anti-diabetic effects of β -glucan from Aureobasidium pullulans were assessed in a streptozotocin (STZ)-induced rat diabetes model at 62.5 and 125 mg/kg doses. In addition, the possibility of changes in the effects of β-glucan according to the severity of diabetes was also assessed at one dosage (62.5 mg/kg): severe, >360 mg/dL; slight, 130-200 mg/dL. Methods: Test articles were administered orally to STZ-induced diabetic rats from 21 days after STZ dosing for 4 weeks. Each of five or six female rats per group was selected using blood glucose levels at 21 days after STZ dosing. Changes in body weight were recorded during the study, along with blood glucose, blood urea nitrogen, creatinine, and serum aspartate aminotransferase and alanine aminotransferase levels. On the day of sacrifice, livers and kidneys were weighed and observed microscopically for changes in the percentage of degenerative regions and numbers of degenerative tubules in the kidney. Results: β-glucan showed no hypoglycemic effects in the STZ-induced diabetic rat model. However, it had favorable effects on decreasing diabetic complications related to diabetic nephropathy and hepatopathy. Conclusion: Based on the results of this study, it was concluded that β-glucan showed favorable effects in decreasing diabetic complications in STZ-induced rat diabetes model.

scholarly journals Distinct Binding Dynamics, Sites and Interactions of Fullerene and Fullerenols with Amyloid-β Peptides Revealed by Molecular Dynamics Simulations

2019 ◽  
Vol 20 (8) ◽  
pp. 2048 ◽  
Author(s):  
Zhiwei Liu ◽  
Yu Zou ◽  
Qingwen Zhang ◽  
Peijie Chen ◽  
Yu Liu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Water Solubility ◽  
Binding Free Energy ◽  
Critical Role ◽  
Amyloid Β ◽  
Fullerene C60 ◽  
Water Soluble ◽  
Hydroxyl Groups ◽  
Dynamics Simulations

The pathology Alzheimer’s disease (AD) is associated with the self-assembly of amyloid-β (Aβ) peptides into β-sheet enriched fibrillar aggregates. A promising treatment strategy is focused on the inhibition of amyloid fibrillization of Aβ peptide. Fullerene C60 is proved to effectively inhibit Aβ fibrillation while the poor water-solubility restricts its use as a biomedicine agent. In this work, we examined the interaction of fullerene C60 and water-soluble fullerenol C60(OH)6/C60(OH)12 (C60 carrying 6/12 hydroxyl groups) with preformed Aβ40/42 protofibrils by multiple molecular dynamics simulations. We found that when binding to the Aβ42 protofibril, C60, C60(OH)6 and C60(OH)12 exhibit distinct binding dynamics, binding sites and peptide interaction. The increased number of hydroxyl groups C60 carries leads to slower binding dynamics and weaker binding strength. Binding free energy analysis demonstrates that the C60/C60(OH)6 molecule primarily binds to the C-terminal residues 31–41, whereas C60(OH)12 favors to bind to N-terminal residues 4–14. The hydrophobic interaction plays a critical role in the interplay between Aβ and all the three nanoparticles, and the π-stacking interaction gets weakened as C60 carries more hydroxyls. In addition, the C60(OH)6 molecule has high affinity to form hydrogen bonds with protein backbones. The binding behaviors of C60/C60(OH)6/C60(OH)12 to the Aβ40 protofibril resemble with those to Aβ42. Our work provides a detailed picture of fullerene/fullerenols binding to Aβ protofibril, and is helpful to understand the underlying inhibitory mechanism.

Terminalia catappa fruit extract reverses streptozotocin- induced diabetic retinopathy in rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Tapan Behl ◽  
Thirumurthy Velpandian ◽  
Anita Kotwani
Keyword(s):  
Diabetic Retinopathy ◽  
Blood Glucose ◽  
Diabetic Rats ◽  
Inflammatory Biomarkers ◽  
Repeated Measure ◽  
Diabetic Rat ◽  
Dependent Manner ◽  
Fruit Extract ◽  
Terminalia Catappa ◽  
Anti Inflammatory

Objective and background: Diabetic retinopathy is amongst the most common microvascular complication associated with diabetes. Controlling blood glucose level alone cannot manage diabetes associated complications. Thus, mechanism that additionally prevent diabetes associated complication are need of the hour, driving the researchers towards herbal therapies. Terminalia catappa is renowned for its anti-inflammatory, antioxidant, anti-hyperglycemic and anti-angiogenic activity. The current study explores the effect of Terminalia catappa fruit extract in streptozotocin-induced diabetic retinopathy in rats. Methods: Streptozotocin-induced chronic diabetic rat model was utilized in the study. Hydro-alcoholic fruit extract of T. catappa in 20mg/kg, 30mg/kg and 40mg/kg dose and standard anti-diabetic drug, glibenclamide (10mg/kg) was given orally. Retinopathy was evaluated by monitoring lenticular, fundus images and measuring arteriole and venule tortuosity index. Oxidative, angiogenic and inflammatory biomarkers were assessed at 12th week in retinal homogenate. Histopathological changes in retina were also examined. Data was analyzed using one-way Repeated Measure ANOVA followed by MannWhitney test. Results: Hydro-alcoholic fruit extract of T. catappa significantly decreased blood glucose (p<0.001) in dose-dependent manner in diabetic rats. Cataract lens was observed in all experimental groups and became clear (grade 0) with 40mg/kg and with 40mg/kg along with glibenclamide at eight and sixth week respectively. Hydro-alcoholic fruit extract in all three doses significantly reduced (p<0.01) arteriole and venule tortuosity in diabetic rats. T. catappa in all three doses in diabetic rats showed modulatory effect in oxidative, angiogenic and inflammatory biomarkers. Conclusion: T. catappa reverses diabetes-induced retinopathy by anti-hyperglycemic, anti-oxidant, anti-angiogenic and anti-inflammatory actions, and thus has a potential to be used in diabetes-induced retinopathy.

scholarly journals Echinacea purpurea Ethanol Extract Improves Male Reproductive Dysfunction With Streptozotocin–Nicotinamide-Induced Diabetic Rats

2021 ◽  
Vol 8 ◽  
Author(s):  
Chien-Feng Mao ◽  
Sabri Sudirman ◽  
Chi-Chih Lee ◽  
David Tsou ◽  
Zwe-Ling Kong
Keyword(s):  
Proinflammatory Cytokines ◽  
Critical Role ◽  
Ethanol Extract ◽  
Echinacea Purpurea ◽  
Diabetic Rats ◽  
Lifestyle Changes ◽  
Male Reproduction ◽  
Reproductive Dysfunction ◽  
Tnf Α ◽  
Anti Inflammatory

As lifestyle changes, the prevalence of diabetes increases every year. Diabetes-induced male reproductive dysfunction is predominantly due to increased oxidative stress and then results in sperm damage and infertility. Echinacea purpurea is a traditional medicinal herb and is well-known for its immune-modulatory, antioxidative, anti-inflammatory, anticancer, and antiviral activities. The Toll-like receptor 4 (TLR4) plays a critical role in innate immune responses leading to nuclear factor (NF)-κB phosphorylation and release of proinflammatory cytokines including nitric oxide (NO), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. However, the relation between Echinacea purpurea extract and TLR4 remains unclear. This study aimed to investigate the protective effects on male reproduction of Echinacea purpurea ethanol extract (EPE) against diabetic rats and whether the anti-inflammatory effects were through the TLR4 pathway. Diabetic male Sprague–Dawley (SD) rats were induced by streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg). EPE was tested in three doses (93, 279, and 465 mg/kg p.o. daily) for 4 weeks. Besides, metformin administration (100 mg/kg/day) was treated as a positive control. Results indicated that EPE administration for about 4 weeks improved hyperglycemia and insulin resistance. Additionally, EPE increased sperm motility, protected sperm morphology and mitochondrial membrane potential, as well as protein for testosterone synthesis enzyme. In sperm superoxide dismutase, catalase, and glutathione antioxidants were increased, whereas proinflammatory cytokines, such as NO, IL-1β, and TNF-α were decreased. The testis protein content of TLR4 and downstream phospho-NF-κB p65 also were reduced. The EPE might reduce the production of proinflammatory cytokines via TLR4 pathways and improve diabetes-induced male infertility.

scholarly journals Endoplasmic reticulum stress is involved in myocardial apoptosis of streptozocin-induced diabetic rats

2007 ◽  
Vol 196 (3) ◽  
pp. 565-572 ◽  
Author(s):  
Zhenhua Li ◽  
Tao Zhang ◽  
Hongyan Dai ◽  
Guanghui Liu ◽  
Haibin Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Diabetic Cardiomyopathy ◽  
Critical Role ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Diabetic Rat ◽  
Mrna Levels ◽  
Diabetic Myocardium

Apoptosis plays a critical role in the diabetic cardiomyopathy, and endoplasmic reticulum stress (ERS) is one of the intrinsic apoptosis pathways. Previous studies have shown that the endoplasmic reticulum becomes swollen and dilated in diabetic myocardium, and ERS is involved in heart failure and diabetic kidney. This study is aimed to demonstrate whether ERS is induced in myocardium of streptozotocin (STZ)-induced diabetic rats. We established a type 1 diabetic rat model, used echocardiographic evaluation, hematoxylin–eosin staining, and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling staining to identify the existence of diabetic cardiomyopathy and enhanced apoptosis in the diabetic heart. We performed immunohistochemistry, western blot, and real-time PCR to analyze the hallmarks of ERS that include glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase12. We found these hallmarks to have enhanced expression in protein and mRNA levels in diabetic myocardium. Also, another pathway that can lead to cell death of ERS, c-Jun NH2-terminal kinase-dependent pathway, was also activated in diabetic heart. Those results suggested that ERS was induced in STZ-induced diabetic rats' myocardium, and ERS-associated apoptosis occurred in the pathophysiology of diabetic cardiomyopathy.

scholarly journals Biocatalytic Approach for Direct Esterification of Ibuprofen with Sorbitol in Biphasic Media

2021 ◽  
Vol 22 (6) ◽  
pp. 3066
Author(s):  
Federico Zappaterra ◽  
Maria Elena Maldonado Rodriguez ◽  
Daniela Summa ◽  
Bruno Semeraro ◽  
Stefania Costa ◽  
...  
Keyword(s):  
Drug Product ◽  
Critical Role ◽  
Water Soluble ◽  
Esterification Reaction ◽  
Enzymatic Esterification ◽  
Porcine Pancreas ◽  
Direct Esterification ◽  
Water Soluble Drug ◽  
Anti Inflammatory ◽  
The 1960S

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) introduced in the 1960s and widely used as an analgesic, anti-inflammatory, and antipyretic. In its acid form, the solubility of 21 mg/L greatly limits its bioavailability. Since the bioavailability of a drug product plays a critical role in the design of oral administration dosage, this study investigated the enzymatic esterification of ibuprofen as a strategy for hydrophilization. This work proposes an enzymatic strategy for the covalent attack of highly hydrophilic molecules using acidic functions of commercially available bioactive compounds. The poorly water-soluble drug ibuprofen was esterified in a hexane/water biphasic system by direct esterification with sorbitol using the cheap biocatalyst porcine pancreas lipase (PPL), which demonstrated itself to be a suitable enzyme for the effective production of the IBU-sorbitol ester. This work reports the optimization of the esterification reaction.

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