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 Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Tingting Jiang ◽  
Qing Chang ◽  
Jiyang Cai ◽  
Jiawen Fan ◽  
Xiaozhe Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Biological Effects ◽  
Interleukin 1 ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Akt Phosphorylation ◽  
Pathogenic Factors ◽  
And Oxidative Stress

Oxidative stress and inflammation are important pathogenic factors contributing to the etiology of diabetic retinopathy (DR). Melatonin is an endogenous hormone that exhibits a variety of biological effects including antioxidant and anti-inflammatory functions. The goals of this study were to determine whether melatonin could ameliorate retinal injury and to explore the potential mechanisms. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Melatonin (10 mg kg−1daily, i.p.) was administered from the induction of diabetes and continued for up to 12 weeks, after which the animals were sacrificed and retinal samples were collected. The retina of diabetic rats showed depletion of glutathione and downregulation of glutamate cysteine ligase (GCL). Melatonin significantly upregulated GCL by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation. The production of proinflammatory cytokines and proteins, including interleukin 1β, TNF-α, and inducible nitric oxide synthase (iNOS), was inhibited by melatonin through the NF-κB pathway. At 12 weeks, melatonin prevented the significant decrease in the ERG a- and b-wave amplitudes under the diabetic condition. Our results suggest potent protective functions of melatonin in diabetic retinopathy. In addition to being a direct antioxidant, melatonin can exert receptor-mediated signaling effects to attenuate inflammation and oxidative stress of the retina.

scholarly journals Curcumin is a Potential Adjuvant to Alleviates Diabetic Retinal Injury via Reducing Oxidative Stress and Maintaining Nrf2 Pathway Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Xie ◽  
Xiaodong Chen ◽  
Wenyi Chen ◽  
Sien Huang ◽  
Xinye Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Early Stage ◽  
Therapeutic Option ◽  
Combined Therapy ◽  
Diabetic Rats ◽  
Receptor Interaction ◽  
Therapeutic Effects ◽  
Hydrogen Atoms ◽  
Nrf2 Pathway ◽  
Retinal Injury

Curcumin is a natural polyphenol compound with anti-diabetic, anti-oxidative, and anti-inflammatory effects. Although many studies have reported the protective effect of curcumin in diabetes mellitus or diabetic nephropathy, there is a lack of research on curcumin in diabetic retinopathy. The purpose of this study was to investigate the therapeutic effects of curcumin on the diabetic retinal injury. Streptozotocin (STZ)-induced diabetic rats (60, n = 12 each) were respectively given curcumin orally (200 mg/kg/day), insulin subcutaneously (4–6 IU/day), and combined therapy with curcumin and insulin for 4 weeks. Retinal histopathological changes, oxidative stress markers, and transcriptome profiles from each group were observed. Curcumin, insulin, or combination therapy significantly reduced blood glucose, alleviated oxidative stress, and improved pathological damage in diabetic rats. Curcumin not only significantly reduced retinal edema but also had a better anti-photoreceptor apoptosis effect than insulin. In the early stage of diabetes, the enhancement of oxidative stress in the retina induced the adaptive activation of the nuclear factor E2-associated factor 2 (Nrf2) pathway. Treatment of curcumin alleviated the compensatory activation of the Nrf2 pathway induced by oxidative stress, by virtue of its antioxidant ability to transfer hydrogen atoms to free radicals. When curcumin combined with insulin, the effect of maintaining Nrf2 pathway homeostasis in diabetic rats was better than that of insulin alone. Transcriptomic analyses revealed that curcumin either alone, or combined with insulin, inhibited the AGE-RAGE signaling pathway and the extracellular matrix (ECM)-receptor interaction in the diabetic retina. Thus, at the early stage of diabetes, curcumin can be used to alleviate diabetic retinal injury through its anti-oxidative effect. If taking curcumin as a potential complementary therapeutic option in combination with antihyperglycemic agents, which would lead to more effective therapeutic outcomes against diabetic complications.

scholarly journals Oxidative Stress in Rats After 60 Days of Hypergalactosemia or Hyperglycemia

2003 ◽  
Vol 22 (6) ◽  
pp. 423-427 ◽  
Author(s):  
Mary Otsyula ◽  
Matthew S. King ◽  
Tonya G. Ketcham ◽  
Ruth A. Sanders ◽  
John B. Watkins
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Glutathione Disulfide ◽  
Hepatic Lipid Peroxidation ◽  
Streptozotocin Diabetic Rats

Two of the models used in current diabetes research include the hypergalactosemic rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies, however, have examined the concurrence of these two models regarding the effects of elevated hexoses on biomarkers of oxidative stress. This study compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and the concentrations of glutathione, glutathione disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation) in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50% galactose diet or insulin deficiency caused by streptozotocin injection. Most rats from both models developed bilateral cataracts. Blood glucose and glycosy-lated hemoglobin A1c concentrations were elevated in streptozotocin diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of streptozotocin-induced diabetic rats normalized altered markers. In galactosemic rats, hepatic lipid peroxidation was increased whereas glutathione reductase activity was diminished. Glutathione levels in liver were decreased in diabetic rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide concentrations were decreased much more in diabetes than in galactosemia. Insulin treatment reversed/prevented all changes caused by streptozotocin-induced diabetes. Lack of concomitance in these data indicate that the 60-day galactose-fed rat is not experiencing the same oxidative stress as the streptozotocin diabetic rat, and that investigators must be cautious drawing conclusions regarding the concurrence of the effects of the two animal models on oxidative stress biomarkers.

scholarly journals Ellagic Acid ameliorates Streptozotocin-Induced Diabetic Hyperalgesia in Rat: Involvement of Oxidative Stress

2021 ◽  
Author(s):  
Siamak Shahidi ◽  
◽  
Alireza Komaki ◽  
Safoura Raoufi ◽  
Iraj Salehi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ellagic Acid ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Antinociceptive Effect ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Tail Flick ◽  
Stress Markers ◽  
Total Antioxidant

Background/Aim: Hyperalgesia is one of the current complications of diabetes mellitus that Oxidative stress and inflammation have principal role in its development. Ellagic Acid (EA) as a herbal component, has some biological activities, including antioxidant and anti-inflammatory effects. This study was designed to evaluate the possible beneficial effect of EA on hyperalgesia in streptozotocin (STZ)-induced diabetic rat. Materials and Methods: Rats were divided into control(vehicle received), diabetic, EA (25, 50 mg/kg)-treated control and EA(25, 50 mg/kg)-treated diabetic groups. Diabetes was induced by a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg/Kg). EA was administered daily by oral gavage for 4 weeks. Hyperalgesia was assessed using tail flick (TF) and hot plate (HP) tests. Also, oxidative stress markers including malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant capacity (TAC) in the serum were evaluated. Results: Diabetic animals showed marked reductions in TF and HP latencies, elevation of serum MDA level and TOS and diminution of serum TAC compared to controls significantly. Treatment of Diabetic rats with EA ameliorated reduction of TF latency at the dose of 25 mg/kg and HP latency at the dose of 50 mg/kg. Furthermore EA significantly increased TAC and decreased MDA level at dose of 50 mg/kg and reduced TOS at both doses in the serum of diabetic animals. In EA treated normal rats we could see no significant alterations in the parameters studied. Conclusion: These results displayed potent antinociceptive effect of EA in diabetic rats via attenuating oxidative stress. This proposes therapeutic potential of EA for damping diabetic hyperalgesia.

scholarly journals An NIR-Triggered Au Nanocage Used for Photo-Thermo Therapy of Chronic Wound in Diabetic Rats Through Bacterial Membrane Destruction and Skin Cell Mitochondrial Protection

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaxin Ding ◽  
Binbin Gao ◽  
Zhenhua Chen ◽  
Xifan Mei
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
Growth Factor ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Human Umbilical Cord ◽  
Bacterial Membrane ◽  
Bacterial Membranes ◽  
Skin Cell ◽  
Diabetic Wounds

Bacterial infection and its severe oxidative stress reaction will cause damage to skin cell mitochondria, resulting in long-lasting wound healing and great pain to patients. Thus, delayed wound healing in diabetic patients with Staphylococcus aureus infection is a principal challenge worldwide. Therefore, novel biomaterials with multifunction of bacterial membrane destruction and skin cell mitochondrial protection are urgently needed to be developed to address this challenge. In this work, novel gold cage (AuNCs) modified with epigallocatechin gallate (EGCG) were prepared to treat delayed diabetic wounds. The results showed that Au-EGCG had a high and stable photothermal conversion efficiency under near-infrared irradiation, and the scavenging rate of Au-EGCG for S. aureus could reach 95%. The production of large amounts of reactive oxygen species (ROS) leads to the disruption of bacterial membranes, inducing bacterial lysis and apoptosis. Meanwhile, Au-EGCG fused into hydrogel (Au-EGCG@H) promoted the migration and proliferation of human umbilical cord endothelial cells, reduced cellular mitochondrial damage and oxidative stress in the presence of infection, and significantly increased the basic fibroblast growth factor expression and vascular endothelial growth factor. In addition, animal studies showed that wound closure was 97.2% after 12 days of treatment, and the healing of chronic diabetic wounds was significantly accelerated. Au-EGCG nanoplatforms were successfully prepared to promote cell migration and angiogenesis in diabetic rats while removing S. aureus, reducing oxidative stress in cells, and restoring impaired mitochondrial function. Au-EGCG provides an effective, biocompatible, and multifunctional therapeutic strategy for chronic diabetic wounds.

scholarly journals Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on Colitis Through PGE2-Mediated T-Cell Modulation

2018 ◽  
Vol 27 (9) ◽  
pp. 1352-1367 ◽  
Author(s):  
Fu Yuan Yang ◽  
Rui Chen ◽  
Xiaohu Zhang ◽  
Biao Huang ◽  
Lai Ling Tsang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Therapeutic Effect ◽  
T Cell Activation ◽  
Activity Index ◽  
Intraperitoneal Administration ◽  
The Body ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration. In this study, we evaluated the effect of preconditioning on the immunoregulatory function of human umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating IBD. Our results show that intraperitoneal administration of deconditioned hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological colitis score and destruction of the epithelial barrier, and increases the body weight recovery more intensively than that of un-manipulated hUCMSCs. In addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction of the ERK pathway during the early stage of IBD development. In vitro co-culture studies indicate that De-hUCMSCs suppress T-cell proliferation and activation more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of inflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is significantly increased in De-hUCMSCs, the suppression of which dramatically abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we have demonstrated that preconditioning enhances the immunosuppressive and therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.

scholarly journals Liraglutide protects cardiac function in diabetic rats through the PPARα pathway

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
Miao Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Cardiac Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Serum Adiponectin ◽  
Diabetic Rat ◽  
Lv Function ◽  
High Dose ◽  
And Oxidative Stress

Increasing evidence shows that diabetes causes cardiac dysfunction. We hypothesized that a glucagon-like peptide-1 (GLP-1) analog, liraglutide, would attenuate cardiac dysfunction in diabetic rats. A total of 24 Sprague–Dawley (SD) rats were divided into two groups fed either a normal diet (normal, n=6) or a high-fat diet (HFD, n=18) for 4 weeks. Then, the HFD rats were injected with streptozotocin (STZ) to create a diabetic rat model. Diabetic rats were divided into three subgroups receiving vehicle (diabetic, n=6), a low dose of liraglutide (Llirag, 0.2 mg/kg/day, n=6), or a high dose of liraglutide (Hlirag, 0.4 mg/kg/day, n=6). Metabolic parameters, systolic blood pressure (SBP), heart rate (HR), left ventricular (LV) function, and whole genome expression of the heart were determined. Diabetic rats developed insulin resistance, increased blood lipid levels and oxidative stress, and impaired LV function, serum adiponectin, nitric oxide (NO). Liraglutide improved insulin resistance, serum adiponectin, NO, HR, and LV function and reduced blood triglyceride (TG), total cholesterol (TC) levels, and oxidative stress. Moreover, liraglutide increased heart nuclear receptor subfamily 1, group H, member 3 (Nr1h3), peroxisome proliferator activated receptor (Ppar) α (Pparα), and Srebp expression and reduced diacylglycerol O-acyltransferase 1 (Dgat) and angiopoietin-like 3 (Angptl3) expression. Liraglutide prevented cardiac dysfunction by activating the PPARα pathway to inhibit Dgat expression and oxidative stress in diabetic rats.

scholarly journals Fortified Extract of Red Berry,Ginkgo biloba, and White Willow Bark in Experimental Early Diabetic Retinopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Claudio Bucolo ◽  
Giuseppina Marrazzo ◽  
Chiara Bianca Maria Platania ◽  
Filippo Drago ◽  
Gian Marco Leggio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Diabetic Retinopathy ◽  
Ginkgo Biloba ◽  
Plasma Lipid ◽  
Thiobarbituric Acid ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
White Willow ◽  
Willow Bark

Diabetic retinopathy is a complex condition where inflammation and oxidative stress represent crucial pathways in the pathogenesis of the disease. Aim of the study was to investigate the effects of a fortified extract of red berries,Ginkgo bilobaand white willow bark containing carnosine andα-lipoic acid in early retinal and plasma changes of streptozotocin-induced diabetic rats. Diabetes was induced by a single streptozotocin injection in Sprague Dawley rats. Diabetics and nondiabetic (control) rats were treated daily with the fortified extract for the ten days. Retina samples were collected and analyzed for their TNF-αand VEGF content. Moreover, plasma oxidative stress was evaluated by thiobarbituric acid reacting substances (TBARS). Increased TNF-αand VEGF levels were observed in the retina of diabetic rats. Treatment with the fortified extract significantly lowered retinal cytokine levels and suppressed diabetes-related lipid peroxidation. These data demonstrate that the fortified extract attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the retina in early diabetic rats.

scholarly journals Spirulina maxima and its effect on antioxidant activity in fructose induced oxidative stress with histopathological observations

2015 ◽  
Vol 62 (2) ◽  
pp. 13-19
Author(s):  
Urmila Jarouliya ◽  
Anish Zacharia ◽  
Raj K. Keservani ◽  
Godavarthi B.K.S Prasad
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Superoxide Dismutase ◽  
Blood Glucose ◽  
Reduced Glutathione ◽  
Thiobarbituric Acid ◽  
Diabetic Rats ◽  
Therapeutic Effects ◽  
Thiobarbituric Acid Reactive Substances ◽  
Spirulina Maxima

Abstract Diabetes mellitus is a metabolic disorder characterised by hyperglycemia and oxidative stress. The aim of the present study is to explore the antioxidant effect of Spirulina maxima in rat model along with the histopathological observations. Diabetes was induced by feeding 10% fructose solution orally to Wistar rats (n = 6) for 30 days, analysed for plasma blood glucose and the markers of the oxidative stress [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)]. These biochemical studies were associated with histopathological examination of liver and kidney sections. The microalga Spirulina maxima being rich in proteins and other essential nutrients is widely used as a food supplement. S. maxima at a dose of 5 and 10% per kg and the metformin (500 mg/kg) as reference drug were given orally for 30 days to the diabetic rats. Diabetic rats showed significant (p < 0.001) elevations in plasma blood glucose, thiobarbituric acid-reactive substances and significant reduction in catalase, superoxide dismutase and reduced glutathione activity. Oral administration of 5 and 10% aqueous extract of S. maxima for 30 days restored not only of blood glucose levels but also markers of oxidative stress. Histopathological observations of tissues manifested that the S. maxima administration had the protective and therapeutic effects against fructose-induced abnormalities in diabetic rats. It is concluded that S. maxima is effective in reinstating the antioxidant activity in addition to its antidiabetic effect in type 2 diabetic rats.

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