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 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 Maslinic Acid Activates Renal Ampk/sirt1 Signaling Pathway to Protect Against Diabetic Nephropathy in Mice

2021 ◽  
Author(s):  
Huijuan Gao ◽  
Hong Wu
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Signaling Pathway ◽  
Acid Treatment ◽  
Diabetic Mouse ◽  
Diabetic Mice ◽  
Pentacyclic Triterpene ◽  
Triterpene Acid ◽  
Maslinic Acid

Abstract BackgroundDiabetic nephropathy has been a devastating complication. Clinically, there is an urgent need for nephroprotective agents to delay the onset of diabetic nephropathy and ameliorate its symptoms. Maslinic acid is a pentacyclic triterpene acid with protective effect on multiple organs from oxidative stress and inflammation. However, the therapeutic effect of maslinic acid on diabetic nephropathy remains unclear.MethodsC57BL/6J male mice administrated with 50 mg/kg of Streptozocin (STZ) daily were used to establish diabetic mouse model (blood glucose levels > 300 mg/dL). Urinary levels of albumin, total proteins, and creatinine were analyzed by an automatic analyzer. H&E staining was used to evaluate renal damage. qRT-PCR and ELISA assay were performed to investigate the inflammation and oxidative stress of renal tissues. Western-blotting assay was used to demonstrate the activation of AMPK signaling.ResultsMaslinic acid treatment alleviated the loss of body weight and blood glucose in diabetic mice. The renal structure and function were protected by maslinic acid in diabetic mice. 20 mg/kg maslinic acid treatment for 8 weeks alleviated the oxidative stress and inflammation in the kidney of diabetic rats dramatically. Maslinic acid treatment activated renal AMPK/SIRT1 signaling.ConclusionMaslinic acid ameliorated diabetic nephropathy via activating AMPK/SIRT1 signaling pathway.

scholarly journals STATISTICAL DATA ANALYSIS WHICH RESULT FROM THE BIO-DIAGNOSIS AND BIO-TREATMENT OF INJURED RATS WITH THE HYPERLIPIDEMIA AND HYPERGLYCEMIA DISEASES

2016 ◽  
Vol 9 (9) ◽  
pp. 122
Author(s):  
Hanan Farouk Aly Abduallah ◽  
Howaida I Abdalla ◽  
Sanaa A Ali ◽  
Mohamed M Mamdooh ◽  
Reda Abo Alez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Liver Function ◽  
Blood Glucose Level ◽  
Lipid Profile ◽  
Glucose Level ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Ipomoea Tricolor ◽  
And Oxidative Stress

ABSTRACTObjective: This study in bioinformatics aims to investigate the potential effect of Ipomoea tricolor and Sophora tomentosa on liver function enzymesactivity, serum lipid profile, oxidative stress biomarkers, and on blood glucose in high fat diet-induced hypercholesterolemia (HC) and STZ-inducedhyperglycemia (HG) in rats.Methods: Blood glucose level, liver function enzymes, alanine aminotransferases and aspartate aminotransferases, alkaline phosphatase, and lactatedehydrogenase (LDH) were determined. Besides, lipid profile including total cholesterol (TC), triacylglycerol (TG), total lipid, and high-densitylipoprotein-cholesterol was investigated. Moreover, oxidative stress biomarkers, lipid peroxide, and nitric oxide as well as non-enzymatic antioxidant,glutathione (GSH) were also examined in different therapeutic groups.Results: A significant increase in blood glucose level, liver function enzyme activities, LDH, lipid profile and oxidative stress markers, while significantdecrease in LDH-C and GSH level in HC-HG induced rats compared to control one. A marked amelioration in all biochemical parameters underinvestigation on treatment of HC-HG rats with I. tricolor and S. tomentosa with different fluctuating percentages of improvement. Histopathologicalexamination of liver and pancreas was also performed and declared HC-HG showed congestion in portal vessels and sinusoids with mild centrilobularhepatocyte degeneration, marked hepatocyte ballooning and hydropic degeneration, while HC-HG treated rats with I. tricolor and S. tomentosa showednormal lobular hepatic architecture with mild sinusoidal dilatation and congestion. On the other hand, a histological organization of pancreas of HC-HGrats showing disarrangement changes in pancreatic blood vessels and interlobular duct as well as disordered in acini. The treatment of HC-HG rats withI. tricolor and S. tomentosa showed enhancement in Langerhans cells and restore of most pancreatic tissue in comparison with standard drugs.Conclusion: The statistical results showed that each extract ameliorated high blood glucose level liver injury, HC and oxidative stress indicatingrelieving of oxidative damage associated with the complexity of HG and HC. These results demonstrated that these two plants extracts may be acandidate intelligent antioxidant, hypolipidemic, hypoglycemic, and hepatoprotective nutraceuticals which need further clinical investigation to beapplied effectively to reduce perturbation in HC associated diabetes.Keywords: Ipomoea tricolor, Sophora tomentosa, Lipid profile and liver function enzymes, Endothelial dysfunction markers, Statistics and imagerecognition, Histopathological analysis.

scholarly journals Reduced HMGB 1-Mediated Pathway and Oxidative Stress in Resveratrol-Treated Diabetic Mice: A Possible Mechanism of Cardioprotection of Resveratrol in Diabetes Mellitus

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Han Wu ◽  
Zhen-Qiang Sheng ◽  
Jun Xie ◽  
Ran Li ◽  
Liang Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Animal Models ◽  
Western Blot ◽  
Signaling Pathway ◽  
Proinflammatory Cytokine ◽  
High Mobility ◽  
Cell Types ◽  
Diabetic Mice ◽  
And Oxidative Stress

Myocardial fibrosis and inflammation are intricately linked in diabetic cardiomyopathy (DCM), and resveratrol has been shown to attenuate oxidative stress, inflammation, and fibrosis in several cell types or animal models. High mobility group box 1 (HMGB 1), a proinflammatory cytokine, has been reported to regulate fibrosis and inflammation in various organs. Then the present study aimed to reveal the expression of HMGB 1-mediated signaling pathway and oxidative stress in resveratrol-treated diabetic mice. The significant increase in serum HMGB 1 concentration in diabetic mice was attenuated by treatment with resveratrol. Similarly, western blot analysis revealed a significant increase of HMGB 1 protein in monocytes and heart tissues of diabetic mice, and resveratrol partly normalized the changes. In addition, resveratrol abrogated the increased expression of HMGB 1-mediated signaling pathway, oxidative stress, fibrosis, and inflammation in diabetic hearts. In conclusion, inhibition of HMGB 1-mediated signaling pathway and oxidative stress may contribute to resveratrol-induced anti-inflammatory and antifibrotic effects in DCM.

scholarly journals Protective Potential of Lycopene Enriched Tomato Extract against Dexamethasone Induced Hepatic and Renal Damage in Mice

2021 ◽  
pp. 1-22
Author(s):  
A. Koul ◽  
J. Kaur ◽  
N. A. Chugh
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Renal Damage ◽  
Cell Damage ◽  
Organ Function ◽  
Protective Potential ◽  
Tomato Extract ◽  
Serum Glutamate ◽  
And Oxidative Stress

Aim: The present study was carried out to determine the protective potential of Lycopene enriched tomato extract (LycT) against hepatic and renal damage caused in mice by dexamethasone administration. Study Design: Male LACA mice were randomly divided into four treatment groups (n=6-7 animals per group) depending upon the treatment they received. Group I (control) animals served as control and were orally administered with olive oil (vehicle) thrice a week for five weeks. Group II (DEX) animals were intraperitoneallly (i.p.) administered with dexamethasone at a dose of 5 mg/kg b.w. on alternate days for three weeks. Group III (LycT) animals were orally (p.o.) administered with LycT at a dose of 5 mg/kg b.w. on alternate days for five weeks. Group IV (LycT+DEX) animals were co-administered with LycT (p.o.) and dexamethasone (i.p.) according to the above mentioned dose regimen Results: Dexamethasone caused hepatic and renal damage as evident from disturbed histoarchitecture, deranged levels of organ function markers (alkaline phosphatase, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, total and direct bilirubin, urea, creatinine) and enhanced level of cell damage (lactate dehydrogenase) and oxidative stress (lipid peroxidation) markers. Increased blood glucose level, decreased hepatic glycogen level along with inhibited activities of enzymes involved in glycolysis (hexokinase, phosphoglucoisomerase) indicated altered glucose metabolism in DEX group. The mitigation in histoarchitectural alterations, cell damage and oxidative stress markers, improved levels of organ function markers, blood glucose level along with ramped up antioxidant defense system indicated the protective potential of LycT against dexamethasone induced ill effects. Conclusions: These results point towards beneficial effects of LycT against dexamethasone induced damage to hepatic and renal tissues in mice.

scholarly journals Assessment of β-Aescin Effect in Streptozotocin Induced Diabetic Model: Diabetic Hepatotoxicity Study

2021 ◽  
pp. 160-168
Author(s):  
Saumya Gupta ◽  
Megha Tiwari ◽  
Vishal Dubey
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Liver Tissue ◽  
Cell Activation ◽  
Estimation Method ◽  
Control Group ◽  
Ros Generation ◽  
Diabetic Mice ◽  
Standard Drug

Objective - Diabetic hepatotoxicity involves complex events which include kupffer cell activation, formation of reactive oxygen species, cytokines release (TNF-α, IL-1β), and finally leads to hepatocyte death. “β- Aescin showed anti-inflammatory, anti-oxidant, gastroprotective and anti-oedema properties. The present study investigated the protective effect of β- Aescin in streptozotocin induced diabetic hepatotoxicity. Method - Female mice were divided into six groups, the first group served as the control, the second to sixth group received single i.p. dose of 90 mg/kg of STZ, the second group served as the untreated diabetic group, the third, fourth and fifth group received β- aescin intra-peritoneally at the dose of 0.9 mg/kg, 1.8 mg/kg and 3.6 mg/kg body weight respectively. The last sixth group was treated with 10 mg/kg glibenclamide i.p. for 14 days. A significant decrease in the blood glucose level was showed in β-aescin group as compared to the control group. Result - A significant increase of blood glucose level was observed in high and mid dose of β- aescin (3.6 mg/kg and 1.8 mg/kg respectively), standard drug (glibenclamide 10 mg/kg) groups as compared to control group. ROS generation was evaluated by using DCF-DA estimation method for the acute toxicity in liver tissue. Streptozotocin group showed more ROS generation in comparison to β- aescin group (3.6 mg/kg). Serum biochemical markers showed a significant decrease in β- aescin treated diabetic mice compared to untreated diabetic mice. Histopathological evaluation showed severe changes in untreated diabetic liver tissue marked by large number of inflammatory cells such as lymphocytes along with hepatic sinusoidal inflammation and hepatocyte necrosis whereas treated diabetic mice with β- aescin showed reduction in hepatotoxicity marked by regeneration changes of hepatocytes and mildly hepatocyte degeneration. Conclusion - In the study, β- aescin showed beneficial effects on the efficient properties of the liver and microscopic improvements in diabetic hepatotoxicity.

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