scholarly journals PO-086 Exercise enhances cardiac antioxidant capacity in diabetic rats through the Keap1/Nrf2 signaling pathway

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Shiqiang Wang
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Diabetic Rats ◽  
Heart Weight ◽  
Stress Injury ◽  
Myocardial Oxidative Stress ◽  
Nrf2 Signaling Pathway ◽  
Gene And Protein Expression

Objective To investigate the effects of exercise on the myocardial oxidative stress injury of diabetic rats, and discussed the role of Keap1/Nrf2 signaling pathway in this process Methods  Tyep 2 diabetic rat model was established by streptozotocin injection through abdominal cavity and high fat diet. The all the diabetic rats were divided into three groups: control group (NC), diabetes group(T2DM) and diabetes exercise group, NC and T2DM group were kept quiet for 8 weeks, T2DME group was trained for 8 weeks. After the exercise, weight, heart weight and blood were measured. MDA, T-SOD and GSH-PX enzyme were measured by biochemical method. Ho-1, Keap1, Nrf2 gene and protein expression were detected by RT-PCR and WesternBlotting. Results Compared with NC group, the weight of rats in the T2DM group significantly decreased [(528+/-71g vs 362+/-33g), P<0.05], HWI  significantly increased [(2.845+/-0.22 vs 3.841+/-0.21, P <0.05], blood glucose was significantly increased [(6.4±3.8 vs 26±7.5mmol/L), P <0.01],T-SOD and GSH-PX activity decreased significantly (P<0.05), Ho-1 protein expression increased (P<0.01), Keap1 and Nrf2 showed no significant changes, and Nrf2 nuclear transposition decreased (P<0.05). Compared with the T2DM group, no significant change in body weight and heart weight in the T2DME group, with significant decrease in HWI[（3.841±0.21 vs 3.235±0.23），P＜0.05], with significant decrease in blood glucose [（26.0±7.5 vs 21.0±6.8），P＜0.05]. Ho-1 gene and protein expression increased significantly（P＜0.05and P＜0.01）, with no significant change of Keap1, while Nrf2 expression increased significantly (P < 0.05), and Nrf2 nuclear transposition increased significantly (P < 0.01). Conclusions Exercise activates the myocardial Keap1/Nrf2 signaling pathway in rats, promotes the expression of downstream antioxidant enzymes, increases cardiac antioxidant capacity, and resists diabetic myocardial oxidative stress injury.

scholarly journals Discovery of Therapeutic Candidates for Diabetic Retinopathy Based on Molecular Switch Analysis: Application of a Systematic Process

2022 ◽  
Vol 2022 ◽  
pp. 1-20
Author(s):  
Yue Ren ◽  
Yanan Liu ◽  
Kaiyang Liu ◽  
Xiaoqian Huo ◽  
Chaoqun Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Vascular System ◽  
System Development ◽  
Molecular Switch ◽  
Stress Injury ◽  
Systematic Process ◽  
Oxidative Stress Injury ◽  
Pathogenic Factors ◽  
Nrf2 Signaling Pathway

The pathogenesis of diabetic retinopathy (DR) is complicated, and there is no effective drug. Oxidative stress-induced human retinal microvascular endothelial cells (HRMECs) injury is one of the pathogenic factors for DR. Molecular switches are considered high-risk targets in disease progression. Identification of molecular switch is crucial to interpret the pathogenesis of disease and screen effective ingredients. In this study, a systematic process was executed to discover therapeutic candidates for DR based on HRMECs injury. First of all, the molecular mechanism of HRMECs oxidative stress injury was revealed by transcriptomics and network pharmacology. We found that oxidative stress was one of the pivotal pathogenic factors, which interfered with vascular system development, inflammation, cell adhesion, and cytoskeleton damaged HRMECs through crosstalk. Then, network topology analysis was used to recognize molecular switches. The results indicated that the Keap1-Nrf2-ARE signaling pathway was the molecular switch in HRMECs oxidative stress injury. On this basis, the HEK293-ARE overexpression cell line was applied to obtain 18 active traditional Chinese medicine (TCM) ingredients. Furthermore, andrographolide, one of the 18 candidates, was applied in the HRMECs oxidative stress model to evaluate the accuracy of the systematic process. The efficacy evaluation results showed that andrographolide could regulate oxidative stress, vascular system development, inflammation, adhesion, and skeleton tissue to inhibit HRMECs injury cooperatively. And its mechanism was related to the Nrf2 signaling pathway. Overall, our data suggest that the Nrf2 signaling pathway is the molecular switch in the HRMECs oxidative stress injury. 18 potential Nrf2 agonists are likely to be promising DR candidates.

scholarly journals Modulation of Renal Insulin Signaling Pathway and Antioxidant Enzymes with Streptozotocin-Induced Diabetes: Effects of Resveratrol

Medicina ◽  
2018 ◽  
Vol 55 (1) ◽  
pp. 3 ◽  
Author(s):  
Gökhan Sadi ◽  
Gamze Şahin ◽  
Aykut Bostanci
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Antioxidant Enzymes ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Diabetic Rats ◽  
Insulin Signaling Pathway ◽  
Enzymatic Antioxidants ◽  
Gene And Protein Expression ◽  
Male Wistar Rats

Background and objectives: Diabetes mellitus is a disease of insulin deficiency or its inability of usage by the target tissues leading to impairment of carbohydrate, lipid, and protein metabolisms. Resveratrol, having robust anti-inflammatory and anti-oxidant properties, has a high potential to treat or prevent the pathogenesis of diseases. This study was conducted to reveal the relationship between diabetes-induced oxidative stress and tissue inflammation with changes in main enzymatic antioxidants (cat, sod, gpx, and gst) and the components of the insulin signaling pathway (insulin Rβ, irs-1, pi3k, akt, mtor) in kidney tissues. Additionally, the effects of resveratrol on these parameters were evaluated. Materials and Methods: Male Wistar rats were randomly divided into four groups; (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; (4) diabetic/20 mg/kg resveratrol. Gene and protein expressions of antioxidant enzymes and insulin signaling elements were evaluated in renal tissues. Results: Downregulation of antioxidant enzymes’ gene expression in the kidney tissues of diabetic rats was demonstrated and this situation was devoted partially to the reduced gene expression of nfκb. Moreover, the components of renal insulin signaling elements were upregulated at both gene and protein expression levels in diabetic rats, and resveratrol treatment decreased this sensitization towards the control state. Conclusion: Resveratrol partially improved diabetes-induced renal oxidative stress and inflammation due to healing action on renal antioxidant enzymes and insulin signaling pathway components.

scholarly journals Hawthorn Leaf Flavonoids Protect against Diabetes-Induced Cardiomyopathy in Rats via PKC-α Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Qing Min ◽  
Yuting Bai ◽  
Yuchen Zhang ◽  
Wei Yu ◽  
Minli Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Blood Glucose ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Cardiac Injury ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Underlying Mechanisms

Objectives. DCM has become one of the main reasons of death in diabetic patients. In this study, we aimed to explore the hawthorn leaf flavonoids (HLF) protective effect against diabetes-induced cardiac injury and the underlying mechanisms in experimental rats. Methods. Experimental diabetic model was induced by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) in rats after feeding with high-fat diet for 8 weeks. The diabetic rats received a 16-week treatment of different doses of HLF (50, 100, and 200). The morphological changes of myocardial cells were observed by light microscope; the concentration of antioxidant indicator and TNF-α and the expression of PKC-α mRNA, PKC-α, and NF-κB proteins were assessed as well. Results. STZ-induced diabetes mellitus prompted blood glucose, cardiac injury, oxidative stress, and inflammation, accompanied with suppressed body weight. On the contrary, HLF administration improved body weight and blood glucose and attenuated myocardial structural abnormalities in diabetic rats. In addition, HLF decreased MDA level and enhanced SOD activities, inhibited TNF-α expression, and downregulated PKC-α mRNA, PKC-α, and NF-κB which were induced by diabetes. Conclusions. HLF has a protective effect against diabetic cardiomyopathy in rats. The mechanism may be involved in reducing oxidative stress and inflammation via inactivation of the PKC-α signaling pathway.

scholarly journals Thymoquinone, the Most Prominent Constituent of Nigella Sativa, Attenuates Liver Damage in Streptozotocin-Induced Diabetic Rats via Regulation of Oxidative Stress, Inflammation and Cyclooxygenase-2 Protein Expression

2021 ◽  
Vol 11 (7) ◽  
pp. 3223
Author(s):  
Saleh A. Almatroodi ◽  
Abdullah M. Alnuqaydan ◽  
Mohammed A. Alsahli ◽  
Amjad Ali Khan ◽  
Arshad Husain Rahmani
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Antioxidant Enzymes ◽  
Blood Glucose ◽  
Liver Function ◽  
Protein Expression ◽  
Inflammatory Markers ◽  
Density Lipoprotein ◽  
Diabetic Rats

Diabetes mellitus (DM) is a multifaceted metabolic disorder that results in dysfunction and failure of various organs. The present study aimed to evaluate the role of Thymoquinone (TQ), on antidiabetic, oxidative stress, and anti-inflammatory activities in streptozotocin (STZ)-induced (55 mg/kg b.w) diabetic rats. TQ was orally given for 8 consecutive weeks at dose of 150 mg/kg b.w. The blood glucose, insulin, total cholesterol, triglycerides, liver function enzymes, high density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol levels were measured accordingly in control, diabetes control (DC), and TQ-treatment groups. These experiments confirmed that TQ conserves the insulin level (0.4 ng/mL vs. 0.23 ng/mL), fasting blood glucose (146 ± 7 mg/dL vs. 225 ± 5 mg/dL), and HbA1c (7.5% vs. 10.6%) quite considerably as compared to DC animals. Our results also confirmed that TQ treatment conserves the body weight and lipid profile significantly in STZ-treated animals as compared to the DC group. Moreover, the antioxidant enzymes (GSH, SOD, GST, and CAT) levels decreased, liver function enzymes (ALT, AST, and ALP), lipid peroxidation and inflammatory markers (TNF-α, CRP, IL-1β, IL-6) increased by STZ treatment, that is significantly restored after TQ treatment. As compared to untreated animals, TQ restored the hepatocytes architectural changes and collagen fibers and cox-2 protein expression in liver tissues as evaluated by hematoxylin and eosin, Masson’s trichrome, and immunohistochemistry staining. Taken together, all these findings indicated that TQ ameliorates glucose level and lipid metabolism. It restores liver function, antioxidant enzymes, anti-inflammatory markers, and maintains hepatocytes architecture in STZ-induced diabetes mellitus rats. Here, in this study, we have demonstrated for the first time the role of TQ in the reduction of the expression of cyclooxygenase-2 and fibrosis formation in diabetic rats. Based on the findings, the study suggests that TQ is a novel natural drug with a wide range of clinical applications including the management of diabetes mellitus.

scholarly journals 6-Gingerol, a Bioactive Compound of Ginger Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats by Regulating the Oxidative Stress and Inflammation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 317
Author(s):  
Saleh A. Almatroodi ◽  
Abdullah M. Alnuqaydan ◽  
Ali Yousif Babiker ◽  
Mashael Abdullah Almogbel ◽  
Amjad Ali Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Blood Glucose ◽  
Protein Expression ◽  
Antioxidant Enzyme ◽  
Renal Damage ◽  
Inflammatory Marker ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Kidney Damage

The aim of present study is to investigate the role of 6-gingerol in ameliorating the renal injury in streptozotocin (STZ)-induced diabetic rats. The diabetes was induced by using a single dose of freshly prepared STZ (55 mg/kg body weight) intraperitoneally which causes the degeneration of pancreatic Langerhans islet β-cells. The diabetic rats were treated with oral gavage of 6-gingerol (10 mg/kg b.w.). The treatment plan was continued for 8 weeks successively and the body weight and fasting blood glucose levels were weekly checked. The biochemical parameters like lipid profile, kidney profile, antioxidant enzyme levels, lipid peroxidation and anti-inflammatory marker levels were investigated after the treatment plant. The pathological condition of kidneys was examined by haematoxylin-eosin (H&E) staining besides this analysis of NF-κB protein expression by immuno-histochemistry was performed. Some of the major parameters in diabetes control vs. normal control were reported as fasting blood glucose (234 ± 10 vs. 102 ± 8 mg/dL), serum creatinine (109.7 ± 7.2 vs. 78.9 ± 4.5 μmol/L) and urea (39.9 ± 1.8 vs. 18.6 mg/dL), lipid profile levels were significantly enhanced in diabetic rats. Moreover, diabetic rats were marked with decreased antioxidant enzyme levels and increased inflammatory markers. Treatment with 6-gingerol significantly restored the fasting blood glucose level, hyperlipidaemia, Malondialdehyde (MDA) and inflammatory marker levels, NF-κB protein expression and augmented the antioxidant enzyme levels in the kidneys of diabetic rats. The kidney damage was significantly normalized by the treatment of 6-gingerol and it provides an evidence that this novel compound plays a significant role in the protection of kidney damage. These findings demonstrate that 6-gingerol reduces lipid parameters, inflammation and oxidative stress in diabetic rats, thereby inhibiting the renal damage. Our results demonstrate that use of 6-gingerol could be a novel therapeutic approach to prevent the kidney damage associated with the diabetes mellitus.

scholarly journals Up-regulation of miR-139-5p protects diabetic mice from liver tissue damage and oxidative stress through inhibiting Notch signaling pathway

2020 ◽  
Vol 52 (4) ◽  
pp. 390-400 ◽  
Author(s):  
Hua Wei ◽  
Liwei Huang ◽  
Fenghua Wei ◽  
Guangzhi Li ◽  
Bin Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Liver Tissue ◽  
Notch Signaling Pathway ◽  
Diabetic Mice ◽  
Stress Injury ◽  
And Oxidative Stress

Abstract The occurrence and development of diabetes seriously threaten the health of patients. Therefore, the mechanism exploration of diabetes is of great significance for more effective control of this disease. In this study, we aimed to investigate the regulatory mechanism of miR-139-5p and Notch signaling pathway on liver damage and oxidative stress in diabetic mice. The mouse model of diabetes was established, and the mice were divided into normal group, model group, negative control (NC) group, miR-139-5p mimic group, miR-139-5p inhibitor group, DAPT group, and miR-139-5p inhibitor + DAPT group. The mRNA expressions of miR-139-5p, Notch1, Jagged1, and NICD1, and the protein expressions of Notch1, Jagged1, and NICD1 were detected. In addition, HepG2 cells were cultured for high glucose induction, and cell cycle distribution and apoptosis were detected by flow cytometry. The results showed that the body weights of mice in the model, NC, miR-139-5p mimic, miR-139-5p inhibitor, DAPT, and miR-139-5p inhibitor + DAPT groups were all lower than that in the normal group. Co-localization of miR-139-5p and Notch1 was observed in the fluorescence in situ hybridization assay, and miR-139-5p was found to negatively regulate Notch1. Furthermore, reduced blood glucose level and inhibited liver oxidative stress were observed in mice with miR-139-5p overexpression or DAPT treatment. DAPT treatment reversed the increase of blood glucose level and oxidative stress injury caused by miR-139-5p silencing. In conclusion, up-regulation of miR-139-5p expression can protect liver tissue from oxidative stress injury in diabetic mice, and its mechanism may be related to the inhibition of Notch signaling pathway.

scholarly journals Huayu Tongluo Recipe Attenuates Renal Oxidative Stress and Inflammation through the Activation of AMPK/Nrf2 Signaling Pathway in Streptozotocin- (STZ-) Induced Diabetic Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yachun Li ◽  
Shuai Guo ◽  
Fan Yang ◽  
Lifei Liu ◽  
Zhiqiang Chen
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Total Protein ◽  
Inflammatory Markers ◽  
Underlying Mechanism ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Nrf2 Signaling Pathway

Diabetic nephropathy (DN), a severe microvascular complication of diabetes, is one of the leading causes of end-stage renal disease. Huayu Tongluo Recipe (HTR) has been widely used in the clinical treatment of DN in China, and its efficacy is reliable. This study aimed to explore the renoprotective effect of HTR and the underlying mechanism. Male Sprague-Dawley rats were fed with high sugar and fat diet combined with an intraperitoneal injection of STZ to establish the diabetic model. Rats in each group were respectively given drinking water, HTR, and irbesartan by gavage for 16 weeks. 24-hour urine samples were collected every 4 weeks to detect the content of total protein and 8-OHdG. Blood samples were taken to detect biochemical indicators and inflammatory markers at the end of 16th week. Renal tissue was collected to investigate pathological changes and to detect oxidative stress and inflammatory markers. AMPK/Nrf2 signaling pathway and fibrosis-related proteins were detected by immunohistochemistry, immunofluorescence, real-time PCR, and western blot. 24h urine total protein (24h UTP), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), and triglyceride (TG) were decreased in the rats treated with HTR, while there was no noticeable change of blood glucose. HTR administration decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in kidneys, complying with reduced 8-OHdG in the urine. The levels of TNF-α, IL-1β, and MCP1 and the expression of nuclear NFκB were also lower after HTR treatment. Furthermore, HTR alleviated pathological renal injury and reduced the accumulation of extracellular matrix (ECM). Besides, HTR enhanced the AMPK/Nrf2 signaling and increased the expression of HO-1 while it inhibited the Nox4/TGF-β1 signaling in the kidneys of STZ-induced diabetic rats. HTR can inhibit renal oxidative stress and inflammation to reduce ECM accumulation and protect the kidney through activating the AMPK/Nrf2 signaling pathway in DN.

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