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. 

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.

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 TBHQ Regulates the Nrf2/HO-1 Pathway to Enhance Stem Cell Treatment of Diabetic Retinopathy

2021 ◽  
Author(s):  
Ze-Peng XU ◽  
Ni TIAN ◽  
Song-Tiao LI ◽  
Kun-Meng LI ◽  
Xiao-Yu WANG ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Therapeutic Effect ◽  
Biological Effects ◽  
Combined Therapy ◽  
Diabetic Rats ◽  
Inflammatory Factors ◽  
Diabetic Rat ◽  
Human Umbilical Cord ◽  
Therapeutic Effects

Abstract Objective: To investigate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic retinopathy (DR) in diabetic rats, and to study the mechanism of hUCMSCs in treating diabetic retinopathy by tert-butylhydroquinone (tBHQ) regulation of the Nrf2/HO-1 pathway.Methods: The diabetic rat model was induced by intraperitoneal injection of streptozotocin (STZ). The experimental animals were divided into six groups: Normal, diabetes mellitus (DM), hUCMSCs, tBHQ, combined tBHQ-hUCMSCs, and all-trans-retinoid acid (ATRA)-hUCMSCs combined group. Visual function experiments and histological analyses were performed eight weeks post intravitreal injection. Biochemical and molecular analyses were used to assess the hUCMSCs composition and its biological effects.Results: Improvements in systemic oxidative stress and inflammation were found in the tBHQ group. Although hUCMSCs had no significant effect on oxidative stress, retinal structure was improved, visual defects reduced and expression of local retinal inflammatory factors were inhibited following its application. The effect of combined therapy was better than that of single therapy. Inhibition of the Nrf2/HO-1 pathway can promote the expression of systemic inflammatory factors and inhibit the therapeutic effect of hUCMSCs in the retina.Conclusions: Intravitreal administration of hUCMSCs triggers an effective cytoprotective microenvironment in the retina of diabetic mice. Alone, however, it may not significantly improve the systemic inflammatory response of diabetes. In combination with tBHQ it may promote Nrf2expression, systemic antioxidant stress and therapeutic effects of hUCMSCs.

scholarly journals Superoxide dismutase 3 prevents early stage diabetic retinopathy in streptozotocin-induced diabetic rat model

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262396
Author(s):  
Ji-Yeon Lee ◽  
Mirinae Kim ◽  
Su Bin Oh ◽  
Hae-Young Kim ◽  
Chongtae Kim ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Diabetic Retinopathy ◽  
Rat Model ◽  
Treated Group ◽  
Diabetic Rats ◽  
Photopic Negative Response ◽  
Diabetic Rat ◽  
Control Group ◽  
Inner Plexiform Layer ◽  
Diabetic Rat Model

Purpose To identify the effects of superoxide dismutase (SOD)3 on diabetes mellitus (DM)-induced retinal changes in a diabetic rat model. Methods Diabetic models were established by a single intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley rats. After purification of the recombinant SOD3, intravitreal injection of SOD3 was performed at the time of STZ injection, and 1 and 2 weeks following STZ injection. Scotopic and photopic electroretinography (ERG) were recorded. Immunofluorescence staining with ɑ-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), pigment epithelium-derived factor (PEDF), Flt1, recoverin, parvalbumin, extracellular superoxide dismutase (SOD3), 8-Hydroxy-2’deoxyguanosine (8-OHdG) and tumor necrosis factor-ɑ (TNF-ɑ) were evaluated. Results In the scotopic ERG, the diabetic group showed reduced a- and b-wave amplitudes compared with the control group. In the photopic ERG, b-wave amplitude showed significant (p < 0.0005) reduction at 8 weeks following DM induction. However, the trend of a- and b-wave reduction was not evident in the SOD3 treated group. GFAP, Flt1, 8-OHdG and TNF-ɑ immunoreactivity were increased, and ɑ-SMA, PEDF and SOD3 immunoreactivity were decreased in the diabetic retina. The immunoreactivity of these markers was partially recovered in the SOD3 treated group. Parvalbumin expression was not decreased in the SOD3 treated group. In the diabetic retinas, the immunoreactivity of recoverin was weakly detected in both of the inner nuclear layer and inner plexiform layer compared to the control group but not in the SOD3 treated group. Conclusions SOD3 treatment attenuated the loss of a/b-wave amplitudes in the diabetic rats, which was consistent with the immunohistochemical evaluation. We also suggest that in rod-dominant rodents, the use of blue on green photopic negative response (PhNR) is effective in measuring the inner retinal function in animal models of diabetic retinopathy. SOD3 treatment ameliorated the retinal Müller cell activation in diabetic rats and pericyte dysfunction. These results suggested that SOD3 exerted protective effects on the development of diabetic retinopathy.

scholarly journals Technological, Sensory, and Hypoglycemic Effects of Quinoa Flour Incorporation into Biscuits

2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Amnah Mohammed Alsuhaibani ◽  
Amal Nassir Alkuraieef ◽  
Moneera Othman Aljobair ◽  
Amal Hassan Alshawi
Keyword(s):  
Chemical Composition ◽  
Wheat Flour ◽  
Glycosylated Hemoglobin ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Total Carotenoids ◽  
Nutritional Values ◽  
Positive Effects ◽  
Quinoa Flour ◽  
Gross Chemical Composition

Background. Biscuits are consumed by all of society in the world. Incorporation of different ratios of quinoa flour into wheat flour for the production of biscuits is needed for the production of functional foods. Objective. This study aimed to evaluate the incorporation of 12.5% or 25% quinoa flour into biscuit production, evaluate rheological and sensory characteristics, and investigate the effect of the consumption of 20% cooked biscuits on diabetic rats. Design. The gross chemical composition, total carotenoids, phenolic and flavonoids of wheat flour and quinoa flour, and the rheological properties of the control, 12.5% quinoa, and 25% quinoa biscuit dough were determined. The effects of consumption of 12.5% quinoa and 25% quinoa biscuits on diabetic rats were investigated. Results. Quinoa flour had significantly higher levels of the gross chemical composition except for carbohydrate and increased phenolic compound and flavonoids content than those in wheat flour. Increasing the amount of quinoa flour in the biscuits could increase the farinograph and extensograph values of the dough. Biological results showed that the highest improvement in nutritional values appeared in the diabetic rat group, which consumed 25% quinoa biscuit for 60 days. The consumption of 12.5% quinoa biscuit and 25% quinoa biscuit showed a decline in blood glycosylated hemoglobin and glucose and an elevation in insulin levels compared with the positive control diabetic rat group. Discussion and Conclusion. It is encouraging to replace wheat flour with quinoa flour in biscuit manufacturing owing to positive effects on both the technological properties and sensory evaluation of biscuits. The increase of quinoa flour up to 25% had favorable nutritional values and hypoglycemic effects.

scholarly journals Candesartan Normalizes Changes in Retinal Blood Flow and p22phox in the Diabetic Rat Retina

2021 ◽  
Vol 28 (1) ◽  
pp. 86-97
Author(s):  
Randa S. Eshaq ◽  
Megan N. Watts ◽  
Patsy R. Carter ◽  
Wendy Leskova ◽  
Tak Yee Aw ◽  
...  
Keyword(s):  
Blood Flow ◽  
Diabetic Retinopathy ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Calcium Release ◽  
Diabetic Rats ◽  
Retinal Blood Flow ◽  
Diabetic Rat ◽  
Angiotensin Ii Receptor ◽  
Tissue Levels

Angiotensin II has been implicated in the progression of diabetic retinopathy, which is characterized by altered microvasculature, oxidative stress, and neuronal dysfunction. The signaling induced by angiotensin II can occur not only via receptor-mediated calcium release that causes vascular constriction, but also through a pathway whereby angiotensin II activates NADPH oxidase to elicit the formation of reactive oxygen species (ROS). In the current study, we administered the angiotensin II receptor antagonist candesartan (or vehicle, in untreated animals) in a rat model of type 1 diabetes in which hyperglycemia was induced by injection of streptozotocin (STZ). Eight weeks after the STZ injection, untreated diabetic rats were found to have a significant increase in tissue levels of angiotensin converting enzyme (ACE; p < 0.05) compared to non-diabetic controls, a 33% decrease in retinal blood flow rate (p < 0.001), and a dramatic increase in p22phox (a subunit of the NADPH oxidase). The decrease in retinal blood flow, and the increases in retinal ACE and p22phox in the diabetic rats, were all significantly attenuated (p < 0.05) by the administration of candesartan in drinking water within one week. Neither STZ nor candesartan induced any changes in tissue levels of superoxide dismutase (SOD-1), 4-hydroxynonenal (4-HNE), or nitrotyrosine. We conclude that one additional benefit of candesartan (and other angiotensin II antagonists) may be to normalize retinal blood flow, which may have clinical benefits in diabetic retinopathy.

scholarly journals Gold Nanoparticle-Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An In Vivo Study in a Diabetic Animal Model

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Saheem Ahmad ◽  
Mohd. Sajid Khan ◽  
Sultan Alouffi ◽  
Saif Khan ◽  
Mahvish Khan ◽  
...  
Keyword(s):  
Microvascular Complications ◽  
Glycosylated Hemoglobin ◽  
Diabetic Animal ◽  
Pancreatic Tissue ◽  
Diabetic Rats ◽  
In Vivo Studies ◽  
Diabetic Rat ◽  
Reactive Carbonyl Species ◽  
Antioxidant Parameters

Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and - N ε -(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.

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 Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Lingli Long ◽  
Yubin Li ◽  
Shuang Yu ◽  
Xiang Li ◽  
Yue Hu ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Oral Administration ◽  
Rat Model ◽  
Microvascular Dysfunction ◽  
Tube Formation ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Diabetic Rat Model

Background. Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. This study demonstrates the antiangiogenic effects of scutellarin (SCU) on high glucose- and hypoxia-stimulated human retinal endothelial cells (HRECs) and on a diabetic rat model by oral administration. The antiangiogenic mechanisms of SCU in vitro and in vivo were investigated. Method. HRECs were cultured in high glucose- (30 mM D-glucose) and hypoxia (cobalt chloride-treated)-stimulated diabetic condition to evaluate the antiangiogenic effects of SCU by CCK-8 test, cell migration experiment (wound healing and transwell), and tube formation experiment. A streptozotocin-induced type II diabetic rat model was established to measure the effects of oral administration of SCU on protecting retinal microvascular dysfunction by Doppler waveforms and HE staining. We further used western blot, luciferase reporter assay, and immunofluorescence staining to study the antiangiogenic mechanism of SCU. The protein levels of phospho-ERK, phospho-FAK, phospho-Src, VEGF, and PEDF were examined in HRECs and retina of diabetic rats. Result. Our results indicated that SCU attenuated diabetes-induced HREC proliferation, migration, and tube formation and decreased neovascularization and resistive index in the retina of diabetic rats by oral administration. SCU suppressed the crosstalk of phospho-ERK, phospho-FAK, phospho-Src, and VEGF in vivo and in vitro. Conclusions. These results suggested that SCU can be an oral drug to alleviate microvascular dysfunction of DR and exerts its antiangiogenic effects by inhibiting the expression of the crosstalk of VEGF, p-ERK, p-FAK, and p-Src.

Anti-diabetic activity of diphenhydramine in diabetic rats

2020 ◽  
Vol 11 (4) ◽  
pp. 5067-5070
Author(s):  
Pang Jyh Chayng ◽  
Nurul Ain ◽  
Kaswandi Md Ambia ◽  
Rahim Md Noah
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Group Iv ◽  
Diabetic Rat ◽  
Control Group ◽  
Group I

The purpose of this project is to study the anti-diabetic effect of on a diabetic rat model. A total of Twenty male Sprague rats were used and it randomly distributed into four groups which are Group I: , Group II: negative control, Group III: and Group IV: and . In diabetic model were induced with via injection at the dosage of 65mg/kg. and FBG (Fasting Blood Glucose) level of diabetic rats were assessed every three days. Blood was collected via cardiac puncture at day 21 after the induction of treatment. Insulin level of the rats was assessed with the Mercodia Rat Insulin ELISA kit. FBG level of group I (12.16 ±3.96, p&lt;0.05) and group IV (11.34 ±3.67, p&lt;0.05) were significantly decreased. Meanwhile, the for all rats did not show any significant increase. However, the insulin level was escalated in group IV (0.74+0.25, p&lt;0.05) significantly. The present study shows that the and the combination of and lowered blood glucose level and enhanced insulin secretion.

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