scholarly journals Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shan Xiao ◽  
Ye Yang ◽  
Yue-Tong Liu ◽  
Jun Zhu
Keyword(s):  
Electron Microscopy ◽  
Diabetic Nephropathy ◽  
Treated Group ◽  
Protective Role ◽  
Control Group ◽  
Related Factors ◽  
Qrt Pcr ◽  
Regulatory Effects ◽  
Tgf Β1 ◽  
Liver Tissues

Purpose. To explore the regulatory effects of liraglutide on the kidney and liver through the miR-34a/SIRT1 pathway with related factors in diabetic nephropathy (DN) rats. Methods. DN rats were randomly divided into two groups ( n = 10 ) and were injected with liraglutide or normal saline twice a day. The 24-hour urine microalbumin content and biochemical index levels were measured. qRT-PCR was performed to detect the expression of miR-34a in the kidney and liver tissues. The levels of SIRT1, HIF-1a, Egr-1, and TGF-β1 in kidney and liver tissues were determined using qRT-PCR, western blot, and immunohistochemistry. Electron microscopy and HE staining were used to observe the ultrastructure and pathological changes. Results. Liraglutide treatment in DN rats decreased blood glucose, 24-hour urine microalbumin, TC, TG, LDL-C, UA, Cr, UREA, ALT, and AST levels and increased the level of HDL-C ( P < 0.05 ). Compared with the control group, the miR-34a levels were significantly decreased in kidney and liver tissues followed by liraglutide treatment ( P < 0.05 ). The levels of SIRT1 in the liraglutide group are significantly higher than those in the control group with the kidney and liver tissues ( P < 0.05 ). Conversely, the contents of HIF-1a, Egr-1, and TGF-β1 were significantly lower in the liraglutide group than in the control group ( P < 0.05 ). Electron microscopy showed that the kidney of the liraglutide-treated group exhibited minor broadening of the mesangial areas, fewer deposits, and a well-organized foot process. HE staining revealed that the kidney of the liraglutide-treated rats had a more regular morphology of the glomerulus and Bowman sac cavity and lighter tubular edema. Additionally, the liraglutide-treated DN rats had a clear hepatic structure, a lower degree of steatosis, and mild inflammatory cell infiltration. Conclusion. Liraglutide, through its effect on the miR-34a/SIRT1 pathway, may have a protective role in the kidney and liver of DN rats.

scholarly journals Knockdown of Angiopoietin-Like Protein 2 Ameliorates Diabetic Nephropathy by Inhibiting TLR4

2017 ◽  
Vol 43 (2) ◽  
pp. 685-696 ◽  
Author(s):  
Suxia Yang ◽  
Junwei Zhang ◽  
Shiying Wang ◽  
Jun Shi ◽  
Xinxin Zhao
Keyword(s):  
Diabetic Nephropathy ◽  
Western Blot ◽  
Inflammatory Cytokines ◽  
Renal Injury ◽  
Collagen Iv ◽  
Pcr Analysis ◽  
Control Group ◽  
Tlr4 Expression ◽  
Qrt Pcr ◽  
Tgf Β1

Background/Aims: Angiopoietin-like protein 2 (ANGPTL2) was reported to be implicated in the pathogenesis of inflammatory disease. Its role in diabetic nephropathy (DN) remained illdefined. Methods: qRT-PCR and western blot analysis were performed to detect the expressions of ANGPTL2 or TLR4 in streptozotocin (STZ)-induced DN rats and HG-stimulated podocytes. The renal injury index including 24-h proteinuria, blood glucose level, serum creatinine and blood urea nitrogen were measured in DN rats using corresponding commercial kits. The effect of ANGPTL2 knockdown on the secretion or expression of inflammatory cytokines was detected by ELISA or qRT-PCR analysis. The effect of ANGPTL2 knockdown on extracellular matrix (ECM) accumulation was determined by testing TGF-β1, Collagen-IV, fibronectin (FN) and PTEN expression via western blot. Results: ANGPTL2 and TLR4 were both highly expressed in DN rats compared with control group. ANGPTL2 knockdown alleviated renal injury in STZ-induced DN rat model. ANGPTL2 knockdown also suppressed inflammatory cytokines (IL-6, TNF-α, MCP-1, IL-1β) expression and ECM accumulation (TGF-β1, Collagen-IV, FN, PTEN) in HG-induced podocytes. Moreover, ANGPTL2 knockdown led to a significant decrease of TLR4 expression in both DN rat and cell model. Furthermore, TAK-242 treatment exacerbated the inhibitory effect of ANGPTL2 knockdown on inflammatory cytokines expression and ECM accumulation in HG-induced podocytes. Conclusion: ANGPTL2 knockdown ameliorates DN by inhibiting TLR4 expression, an observation contributing to a better understanding of DN pathogenesis.

scholarly journals The effect of vitamin C on Endosulfan-induced oxidative stress parameters in prepubertal rats

Biomedicine ◽  
2020 ◽  
Vol 39 (2) ◽  
pp. 333-338
Author(s):  
Kalaivani Manokaran ◽  
Vasanthalaxmi Krishnananda Rao ◽  
Nilima . ◽  
Manjula Shimoga Durgoji Rao ◽  
Sucheta Prasanna Kumar
Keyword(s):  
Oxidative Stress ◽  
Vitamin C ◽  
Wistar Rats ◽  
Statistical Significance ◽  
Treated Group ◽  
Reproductive Organs ◽  
Protective Role ◽  
Control Group ◽  
Group I ◽  
Testicular Weight

Introduction and Aim: Oxidative stress plays a very important role in endosulfan-induced toxic effects on reproductive organs. Vitamin C is a potent antioxidant which plays an important role in decreasing oxidative stress. The present study was aimed to investigate the protective role of vitamin C against endosulfan-induced testicular toxicity in Wistar rats. To investigate a protective effect of vitamin C against endosulfan induced toxicity on biochemical changes. Materials and Methods: Seventy male neonatal Wistar rats were divided into  seven groups. The group  I was taken as the control group, the endosulfan-treated were grouped into II (3 mg/kg body weight (BW) and group III (6 mg/kg BW), Group IV (9 mg/kg BW) and Group V (12 mg/kg BW). Group VI (9 mg/kg BW) and group VII (12 mg/kg BW) were pretreated with vitamin C (20 mg/kg BW) for 60 days. After  the experimental procedures, the testicular weight, lactate dehydrogenase (LDH) enzyme and testosterone in plasma, LDH, steroidogenic enzymes 3?-HSD and 17?-HSD in testis were evaluated. One-way ANOVA was used to determine the statistical significance. Results: Significant improvement in the testicular weight (P<0.05) , LDH (P<0.05) levels both in plasma and testis, increase in testosterone(P<0.001) and steroidogenic enzyme levels(P<0.001) was observed in the group pretreated with vitamin C treated group when compared to the endosulfan treated group. Conclusion: Vitamin C decreases the toxic effect of endosulfan on testis. The present action might be  due to its antioxidative properties.

scholarly journals Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control

2007 ◽  
Vol 22 (5) ◽  
pp. 337-341 ◽  
Author(s):  
Célia Sperandéo Macedo ◽  
Mauro Masson Lerco ◽  
Sônia Maria Capelletti ◽  
Reinaldo José Silva ◽  
Daniela de Oliveira Pinheiro ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Body Weight ◽  
Diabetic Nephropathy ◽  
Glycemic Control ◽  
Wistar Rats ◽  
Treated Group ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Gbm Thickening ◽  
Diabetes Induction

PURPOSE: To determine podocyte number and GBM thickness in diabetic rats either under glycemic control or without glycemic control at 6 and 12 months after diabetes induction. METHODS: 100 wistar rats weighing 200-300g were divided into 6 groups: Normal group (N6 and N12- 25 rats); Diabetic group (D6 and D12- 25 rats), diabetic treated group ( DT 6 and DT 12- 25 rats) on insulin 1,8- 3,0 IU/Kg associated with acarbose (50mg to 100g of food) daily mixed in chow. Alloxan was injected intravenously in a dose of 42 mg/Kg of weight. Body weight, waterintake, 24-h diuresis, glycemia and glucosuria were determined before induction, 7 and 14 days after induction and monthly thereafter. Treatment started at day 14. Three groups were sacrificed at 6 months (N6,D6, DT6) and 3 groups at 12 months (N12, D12, DT12) with the renal tissue being prepared for electron microscopy. RESULTS: Glycemia in DT6¨and in DT12 was significantly different from that in D6 and D12 rats and similar to that in N6 and N12 animals. The number of podocytes in DT6 was not different from that in N6 and D6 (median = 11); the number of podocytes in DT12 (median = 11) differed from that in D12 (median = 8), but not from that in N12 (median = 11). GBM thickness in D6 (0.18 micrometers) was lower than in D12 (0.29 micrometers); while in DT6 (0.16 micrometers) it was lower than in D6 (0.18 micrometers). In DT12 (0.26 micrometers), it was lower than in D12 (0.29 micrometers). CONCLUSION: The control of hyperglycemia prevented GBM thickening in early and late (12 mo) alloxan diabetic nephropathy and podocyte number reduction.

Protective role of low-dose TGF-β1 in early diabetic nephropathy induced by streptozotocin

2013 ◽  
Vol 17 (3) ◽  
pp. 752-758 ◽  
Author(s):  
Xiaodong Ma ◽  
Jingjing Ding ◽  
Haiyan Min ◽  
Yanting Wen ◽  
Qian Gao
Keyword(s):  
Diabetic Nephropathy ◽  
Low Dose ◽  
Protective Role ◽  
Early Diabetic Nephropathy ◽  
Tgf Β1

scholarly journals Protective role of ceftriaxone plus sulbactam with VRP1034 on oxidative stress, hematological and enzymatic parameters in cadmium toxicity induced rat model

2012 ◽  
Vol 5 (4) ◽  
pp. 192-200 ◽  
Author(s):  
Vivek Kumar Dwivedi ◽  
Anuj Bhatanagar ◽  
Manu Chaudhary
Keyword(s):  
Free Radical ◽  
Tissue Injury ◽  
Cadmium Toxicity ◽  
Treated Group ◽  
Protective Role ◽  
Enzymatic Activities ◽  
Exposed Group ◽  
Male Rats ◽  
Control Group

ABSTRACT We investigated the protective role of ceftriaxone plus sulbactam with VRP1034 (Elores) on hematological, lipid peroxidation, antioxidant enzymatic activities and Cd levels in the blood and tissues of cadmium exposed rats. Twenty-four male rats were divided into three groups of eight rats each. The control group received distilled water whereas group II received CdCl2 (1.5 mg/4 ml/body weight) through gastric gavage for 21 days. Group III received CdCl2 and was treated with ceftriaxone plus sulbactam with VRP1034 for 21 days. The hematological, biochemical, lipid per-oxidation levels and enzymatic parameters were measured in plasma and tissues (brain, liver and kidney) of all groups. The Cd, Zn and Fe levels were measured in blood and tissues of all groups. Our findings showed significantly decreased cadmium (p<0.001), malonaldialdehyde (p<0.001) and myloperoxidase (MPO) levels along with significantly increased hemoglobin (p<0.01), RBC (p<0.05), hematocrit (p<0.05) levels and all antioxidant enzymatic activities (SOD, CAT, GR, GPx) in plasma and tissues of ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. Delta aminolevulinate dehydratase (δ-ALAD) activity was significantly (p<0.001) increased in the blood of ceftriaxone plus sulbactam with VRP1034 treated group as compared with cadmium exposed group. The levels of hepatic and renal parameters were significantly (p<0.001) decreased in ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. These findings indicate that ceftriaxone plus sulbactam with VRP1034 acts as a potent free radical scavenger and exhibits metal chelating properties that reduce free radical mediated tissue injury and prevent dysfunction of hepatic and renal organs during metal intoxication.

Overexpressed microRNA-141-3p enhance proliferation via targeting PLAG1 in non-diabetic macrosomia

2018 ◽  
Author(s):  
Dan Guo ◽  
Hua Jiang ◽  
Yiqiu Chen ◽  
Jing Yang ◽  
Ziqiang Fu ◽  
...  
Keyword(s):  
Target Gene ◽  
Late Pregnancy ◽  
Treated Group ◽  
Control Group ◽  
Placental Development ◽  
Mirna Microarray ◽  
Qrt Pcr ◽  
Significant Difference ◽  
Fetal Birth Weight ◽  
Proliferation And Invasion

AbstractSeveral studies have shown microRNAs (miRNAs) could regulate the placental development, yet the role and mechanism of miRNAs in the development of non-diabetic macrosomia (NDFMS) remains unclear. The key miRNA that abnormal expressed in NDFMS placentas was screened out by miRNA microarray and verified using qRT-PCR in 91 subjects. The effects of the key miRNA were verified by proliferation assay and invasion assay in HTR-8/SVneo cell, and also in pregnant C57BL/6J mice. miR-141-3p was determined as the key miRNA with the most significant difference, which could promote the proliferation and invasion by regulating the expression of target gene PLAG1. Overexpression of PLAG1 could reverse the effect of cell proliferation and invasion ability caused by miR-141-3p overexpression. Significant difference in fetal birth weight was observed between the control group and treated group with miR-141-3p agomir in late pregnancy, but not in early pregnancy. This study revealed miR-141-3p could increase the proliferation of placenta to participate in the occurrence and development of NDFMS through regulating PLAG1 expression.

scholarly journals Staphylococcus aureus Infection Induced Oxidative Imbalance in Neutrophils: Possible Protective Role of Nanoconjugated Vancomycin

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Subhankari Prasad Chakraborty ◽  
Panchanan Pramanik ◽  
Somenath Roy
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Cell Damage ◽  
Treated Group ◽  
Protective Role ◽  
Control Group ◽  
Similar Dose ◽  
Cellular Components

Staphylococcus aureus infection causes oxidative stress in neutrophils. The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was aimed to test the protective role of nanoconjugated vancomycin against vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection induced oxidative stress in neutrophils. VSSA- and VRSA-infection were developed in Swiss mice by intraperitoneal injection of 5×106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was treated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was treated to VSSA and VRSA infected mice at similar dose, respectively, for 10 days. The result reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, and nitrite generation and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group; which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These finding suggests the potential use and beneficial protective role of nanoconjugated vancomycin against VSSA and VRSA infection induced oxidative imbalance in neutrophils.

scholarly journals Hydrogen sulfide prevents arterial medial calcification in rats with diabetic nephropathy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fang-Zheng Wang ◽  
Hong Zhou ◽  
Hong-Yu Wang ◽  
Hang-Bing Dai ◽  
Qing Gao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Hydrogen Sulfide ◽  
Calcium Deposition ◽  
Control Group ◽  
Sprague Dawley ◽  
Sodium Hydrosulfide ◽  
Key Factor ◽  
Tgf Β1 ◽  
Arterial Medial Calcification ◽  
Medial Calcification

Abstract Background Arterial medial calcification (AMC) is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes and chronic kidney disease. Here, we tested whether hydrogen sulfide (H2S) can prevent AMC in rats with diabetic nephropathy (DN). Methods DN was induced by a single injection of streptozotocin and high-fat diet (45% kcal as fat) containing 0.75% adenine in Sprague–Dawley rats for 8 weeks. Results Rats with DN displayed obvious calcification in aorta, and this was significantly alleviated by Sodium Hydrosulfide (NaHS, a H2S donor, 50 μmol/kg/day for 8 weeks) treatment through decreasing calcium and phosphorus content, ALP activity and calcium deposition in aorta. Interestingly, the main endogenous H2S generating enzyme activity and protein expression of cystathionine-γ-lyase (CSE) were largely reduced in the arterial wall of DN rats. Exogenous NaHS treatment restored CSE activity and its expression, inhibited aortic osteogenic transformation by upregulating phenotypic markers of smooth muscle cells SMα-actin and SM22α, and downregulating core binding factor α-1 (Cbfα-1, a key factor for bone formation), protein expressions in rats with DN when compared to the control group. NaHS administration also significantly reduced Stat3 activation, cathepsin S (CAS) activity and TGF-β1 protein level, and improved aortic elastin expression. Conclusions H2S may have a clinical significance for treating AMC in people with DN by reducing Stat3 activation, CAS activity, TGF-β1 level and increasing local elastin level.

scholarly journals miR-92d-3p suppresses the progression of diabetic nephropathy renal fibrosis by inhibiting the C3/HMGB1/TGF-β1 pathway

2021 ◽  
Author(s):  
Yuhua Zhang
Keyword(s):  
Animal Model ◽  
Diabetic Nephropathy ◽  
Renal Fibrosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Factor ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Tnf Α ◽  
Tgf Β1 ◽  
E Cadherin

The pathogenesis of diabetic nephropathy (DN) has not been fully elucidated. MicroRNAs play an important role in the onset and development of DN renal fibrosis. Thus, this study aimed to investigate the effect of miR-92d-3p on the progression of DN renal fibrosis. We used qRT-PCR to detect the expression levels of miR-92d-3p in the kidneys of patients with DN. Then, after transfecting lentiviruses containing miR-92d-3p into the kidneys of a DN mouse model and HK-2 cell line, we used qRT-PCR to detect the expression levels of miR-92d-3p, C3, HMGB1, TGF-β1, α-SMA, E-cadherin, and Col Ⅰ. The expression levels of IL-1β, IL-6, and TNF-α in the HK-2 cells were detected through enzyme-linked immunosorbent assay, and Western blotting and immunofluorescence were used in detecting the expression levels of fibronectin, α-SMA, E-cadherin, and vimentin. Results showed that the expression levels of miR-92d-3p in the kidney tissues of patients with DN and DN animal model mice decreased, and C3 stimulated HK-2 cells to produce inflammatory cytokines. The C3/HMGB1/TGF-β1 pathway was activated, and EMT was induced in the HK-2 cells after human recombinant C3 and TGF-β1 protein were added. miR-92d-3p inhibited inflammatory factor production by C3 in the HK-2 cells and the activation of the C3/HMGB1/TGF-β1 pathway and EMT by C3 and TGF-β1. miR-92d-3p suppressed the progression of DN renal fibrosis by inhibiting the activation of the C3/HMGB1/TGF-β1 pathway and EMT.

scholarly journals Shengu'an exerts anti-osteoporotic effect in rats via TGFβ1-Smad2/3 signal pathway, and enhancement of bone and cartilage metabolism

2020 ◽  
Vol 19 (6) ◽  
pp. 1191-1196
Author(s):  
Wei Li ◽  
Zhiqiang Peng ◽  
Yulun Wu ◽  
Jintao Hu ◽  
Peilun Li ◽  
...  
Keyword(s):  
Vertebral Body ◽  
Transforming Growth Factor ◽  
Treated Group ◽  
Transforming Growth Factor Β1 ◽  
Signal Pathway ◽  
Control Group ◽  
Cartilage Metabolism ◽  
Platelet Endothelial Cell Adhesion ◽  
Healthy Female ◽  
Tgf Β1

Purpose: To study the anti-osteoporotic effect of Shengu'an in rats, and elucidate the mechanism of action involved.Methods: Forty healthy female SPF mice were randomly divided into control group, saline-treated group, TGFβRⅡ receptor inhibitor group, and shengu'an group. The expressions of type Ⅱ collagen (Co1-II) and platelet endothelial cell adhesion factor (CD-31) were determined. The expressions of transforming growth factor β1 (TGF-β1), p-smad2/3, matrix metalloproteinase-9 (MMP-9) and osteoblast specific transcription factor (osterix) were assayed by western blotting.Results: The expression of Co1-II in the vertebral body was significantly lower in model mice than in control mice, but was significantly higher in shengu'an mice when compared with model mice (p < 0.05). In shengu'an mice, CoI-I was markedly upregulated, relative to model mice, and the expressions of CD31 in TGFβRⅡreceptor inhibitor group and shengu'an group were lower than in model group (p < 0.05). There were significantly lower expressions of TGF-β1 and p-smad2/3 in the vertebral body of shengu'an group than in model mice, but osterix was upregulated relative to model mice (p < 0.05).Conclusion: Shengu'an exerts anti-osteoporotic effect by downregulating TGFβ/smad signal pathway. There is thus a potential for its clinical application in the management of osteoporosis. Keywords: Shengu'an, TGFβ1-Smad2/3 signal, Bone cartilage metabolism, Osteoporosis

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