Recombinant annexin-2 inhibits the progress of diabetic nephropathy in a diabetic mouse model via recovery of hypercoagulability

2007 ◽  
Vol 97 (01) ◽  
pp. 124-128 ◽  
Author(s):  
Hideto Ishii ◽  
Megumi Hiraoka ◽  
Akira Tanaka ◽  
Kentaro Shimokado ◽  
Masayuki Yoshida
Keyword(s):  
Endothelial Cells ◽  
Diabetic Nephropathy ◽  
Major Complication ◽  
Coagulation System ◽  
Control Group ◽  
Protective Effects ◽  
Kidney Size ◽  
Annexin 2 ◽  
Glomerular Lesions ◽  
Ay Mice

SummaryDiabetic nephropathy, a major complication of diabetes mellitus that leads to mortality, has been shown to involve a dysregulation of the coagulation system. Annexin-2, a co-receptor for plasminogen and tissue plasminogen activator on endothelial cells, is one of the molecules required to maintain the antithrombogenic properties of endothelial cells. Previously, we showed that recombinant annexin-2 protein (rAN II) modulated impaired fibrinolytic activity in the carotid arteries of rats. In the present study, to investigate its protective effects against diabetic nephropathy, rAN II was administered to KK-Ay mice, a murine model of type 2 diabetes, for eight weeks, and albuminuria, kidney size, and histological glomerular lesions were investigated. The mean weight of kidneys from KK-Ay mice treated with rAN II was significantly less than that of those treated with PBS (control) (p<0.02). Furthermore, the level of albuminuria observed in rAN II-treated KK-Ay mice was significantly less than that of the control group (rAN II, 0.90+/-0.12 µg/day; PBS, 1.55+/-0.31 µg/day; p<0.01); also, the area of diffuse glomerular lesions was significantly smaller (rAN II, 41.51+/-4.54%; PBS, 81.81+/-8.10%; p<0.01). Bleeding time, prothrombin time (PT), and active partial thromboplastin time (APTT) did not significantly differ between the two groups. Our results suggest that rAN II may inhibit the progression of diabetic nephropathy in KK-Ay mice without influencing the coagulation system, indicating that annexin-2 may be considered as a possible new therapeutic tool for patients with diabetic nephropathy.

Protective effect of three developed gel formulations: Chitosan, Chitosan with Taurine and Chitosan with Dexpanthenol, on the acute overdose of Diclofenac sodium in preclinical studies

2021 ◽  
pp. 4341-4348
Author(s):  
Solaiman Doba ◽  
Anna Buzlama
Keyword(s):  
Intestinal Inflammation ◽  
Diclofenac Sodium ◽  
Male Rats ◽  
Coagulation System ◽  
Control Group ◽  
Protective Effects ◽  
Blood Samples ◽  
The Third ◽  
Acute Overdose ◽  
Gel Formulations

Objectives: To investigate the tissue-protective effects of three gel formulations (chitosan, chitosan with taurine or chitosan with dexpanthenol) as active substances against an acute overdose of diclofenac sodium. Methods: White outbred conventional male rats were allocated to five experimental groups: the first is an intact group that did not receive any drug, the second group is a control group that received 50mg/kg of diclofenac sodium once orally, the third, fourth and fifth groups are an experimental group that received our studied drugs at a dose of 0.16ml/100mg b.w. once orally 1 hr. before diclofenac sodium, the third group received chitosan-based gel 1%, the fourth group received chitosan-based gel 1% with 4% taurine and the fifth group chitosan-based gel 1% with 0.43% dexpanthenol. Blood samples were taken for biochemical, hematological and blood coagulation system tests on day 7th after administration of diclofenac sodium. Results: An acute overdose of diclofenac sodium caused marked extensive tissue necrosis in the liver, bleeding in the gastrointestinal tract and inflammatory process, these marks were evidenced by different changes in the test of the blood samples. Significantly 73.6% of the blood indicators were improved by the administration of chitosan-based gel 1% with 0.43% dexpanthenol, while 57.8% were improved by chitosan-based gel 1% with 4% taurine and 68.4% by chitosan-based gel 1%. Conclusion: Chitosan-based gel 1% with dexpanthenol 0.43% can help in mitigating hepatic injury, gastrointestinal bleeding, and systemic and local intestinal inflammation caused by an acute overdose of diclofenac sodium.

scholarly journals Protective effects of specneuzhenide on renal injury in rats with diabetic nephropathy

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 740-747
Author(s):  
Jiangning Yin ◽  
Jun Jiang ◽  
Huajun Wang ◽  
Guoyuan Lu
Keyword(s):  
Body Weight ◽  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Low Dose ◽  
High Dose ◽  
Protective Effects ◽  
Model Group ◽  
Urine Protein ◽  
Tnf Α ◽  
Glomerular Lesions

AbstractBackgroundWe aim to investigate the protective effects and potential mechanisms in specneuzhenide (SPE) on renal injury in rats with diabetic nephropathy (DN).ResultsSPE could inhibit the decrease of body weight compared with the model group (P<0.05), and trigger improvement in the renal index (P<0.05). High dose and low dose SPE could trigger a significant decrease in serum IL1β, IL-6 and TNF-α compared with the model group (P<0.05). SPE could attenuate the glomerular lesions in DN rats. SPE induced up-regulation of podocin and CD2AP (P<0.05).ConclusionSPE showed protective effects on renal injury through attenuating the pathological injury and urine protein. This process may be closely related to the modulation of CD2AP and podocin expression.

scholarly journals Effects of Lentinan on Endothelial Cell Activity, Inflammatory Response, Endoplasmic Reticulum Stress, and Apoptosis in Sepsis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yan Xu ◽  
Yeping Du
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Activity ◽  
Sepsis Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Protective Effects

The aim of this study is to explore the protective effects of lentinan on endoplasmic reticulum stress, inflammation, and apoptosis in sepsis endothelial cells. Firstly, lentinan was extracted, purified, and analyzed. When the concentration of lentinan was in the range of 0.04–4 μM, there was no obvious effect on the morphology of HUVECs. When the concentration reached 10 M, the cells were obviously contracted and necrotic. CCK-8 cell activity experiment showed that when the concentration of lentinan reached 4 μM, the cell activity decreased significantly (P<0.001), and it was in a dose-dependent manner. Then, the cells were divided into the control group (0 μM lentinan), sepsis group, sepsis + lentinan 1.2 μM group, and sepsis + lentinan 2 μM group. Enzyme-linked immunosorbent assay showed that lentinan could significantly reduce the expression of TNF-α, IL-1β, and IL-6 in sepsis endothelial cells (P<0.001). In addition, flow cytometry and TUNEL staining showed that compared with the control group, the apoptosis of cells in the sepsis group increased significantly (P<0.001), and lentinan could inhibit apoptosis (P<0.001). In terms of mechanism research, the mRNA and protein expression of endoplasmic reticulum stress-related protein in endothelial cells were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting, respectively. It was found that the expression of SIRT1, the upstream factors of endoplasmic reticulum stress in sepsis cells, was obviously inhibited (P<0.001), and the expression of CHOP, GRP78, IRE1α, and ATF6 was significantly increased (P<0.001), However, the pretreatment of lentinan could significantly reverse the above changes (P<0.001). Besides, lentinan could also reduce the expression of phosphorylated p65 protein (the activation marker of NF-κb) and iNOS. Conclusion. When sepsis occurs, lentinan can protect endothelial cells from ERS inflammation and apoptosis induced by sepsis. Thus, lentinan is expected to be a new target for the treatment of sepsis-induced endothelial damage.

P0984SGLT2 INHIBITION PREVENTS RENAL FIBROSIS IN CYCLOSPORINE NEPHROPATHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Giovanna Castoldi ◽  
Raffaella Carletti ◽  
Silvia Ippolito ◽  
Massimiliano Colzani ◽  
Francesca Barzaghi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Tyrosine Hydroxylase ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Control Group ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Type 2 Diabetic Patients ◽  
Inflammatory Infiltrates

Abstract Background and Aims Sodium glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic drugs, showed nephroprotection in type 2 diabetic patients. The mechanisms underlying nephroprotection are not completely known and it is unclear whether the nephroprotective effects are present also in non-diabetic nephropathy. The aim of this study was to evaluate the effects of empagliflozin, a SGLT-2 inhibitor, in cyclosporine nephropathy in the absence of diabetes. Method Ten days before the beginning and then during the entire experimental periods, low-salt diet (Teklad 7034) was administered to Sprague Dawley rats. Cyclosporine-A (CsA, 15 mg/kg/day, intraperitoneal injection; n=6) and CsA plus empagliflozin (Empa, 10 mg/kg /day, per os; n=6) were administered for 4 weeks. Control group was treated with placebo (n=6). Blood pressure was measured by plethysmographic method at the beginning and at the end of the experimental period. At the end of the protocol, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and tyrosine hydroxylase expression, used as marker of symphatetic nerve activity. Results The rats treated with CsA showed a significant increase (p &lt;0.01) in blood pressure, which was slightly reduced by administration of empagliflozin. CsA administration caused an increase in glomerular and tubulo-interstitial fibrosis (p &lt;0.05), renal inflammatory infiltrates (p &lt;0.05) and tyrosine hydroxylase expression (p &lt;0.01) as compared to the control rats. Treatment with empagliflozin reduced glomerular and tubulo-interstitial fibrosis (p &lt;0.05), inflammatory cell infiltration (p &lt;0.01) and tyrosine hydroxylase expression (p &lt;0.01), as compared to CsA-treated rats. Conclusion Empagliflozin administration showed protective effects on cyclosporine nephropathy, decreasing renal fibrosis, macrophage infiltration and tyrosine hydroxylase expression. These data suggest that the nephroprotective role of empagliflozin could not be restricted only to diabetic nephropathy.

scholarly journals SIRT1-Mediated Protective Effect of Aralia elata (Miq.) Seem against High-Glucose-Induced Senescence in Human Umbilical Vein Endothelial Cells

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2625
Author(s):  
Gi Dae Kim
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
High Glucose ◽  
Umbilical Vein ◽  
Control Group ◽  
Protective Effects ◽  
Aging Effects ◽  
Human Umbilical Vein ◽  
Aralia Elata ◽  
Umbilical Vein Endothelial Cells

Aralia elata (Miq.) Seem (AS) is widely been for treating many diseases, enhancing energy, and boosting immunity; however, its protective effects against high-glucose (HG)-triggered endothelial dysfunction and the potential underlying mechanisms have not been investigated. In this study, we determined the effect of AS on senescence in human umbilical vein endothelial cells (HUVECs) and elucidated the mechanisms underlying its anti-aging effects. The senescence model of endothelial cells (ECs) was established by culturing HUVECs in media containing HG (30 mM). We found that the proportion of senescent (senescence-associated β-galactosidase+) cells in the HG group was significantly higher than that in the control group; however, this increase was suppressed by AS treatment. Moreover, cell cycle analysis revealed that AS (20 μg/mL) significantly recovered HG-induced cell cycle arrest in ECs, and Western blot revealed that AS prevented HG-induced decreases in silent information regulator 1 (SIRT1) level and endothelial nitric oxide synthase (eNOS) phosphorylation. These results show that AS delayed HG-induced senescence in ECs by modulation of the SIRT1/5′ AMP-activated protein kinase and AKT/eNOS pathways.

scholarly journals Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jang Hyun Koh ◽  
Eun Soo Lee ◽  
Miri Hyun ◽  
Hong Min Kim ◽  
Yoon Jung Choi ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Insulin Secretion ◽  
Glucose Level ◽  
Rat Model ◽  
Diabetic Rat ◽  
Control Group ◽  
Protective Effects ◽  
Oletf Rats ◽  
Antioxidant Effects

The overexpression of vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10), OLETF rats as diabetic control group (n=10), and OLETF rats treated with taurine group (n=10). We treated taurine (200 mg/kg/day) for 20 weeks and treated high glucose (HG, 30 mM) with or without taurine (30 mM) in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS) levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.

Protective effects of soy-isoflavones in cardiovascular disease

2008 ◽  
Vol 28 (01/02) ◽  
pp. 85-88 ◽  
Author(s):  
D. Fuchs ◽  
H. Daniel ◽  
U. Wenzel
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Dietary Intervention ◽  
Mononuclear Cells ◽  
Oxidized Ldl ◽  
Proteome Analysis ◽  
Soy Isoflavones ◽  
Protective Effects ◽  
Estrogen Production

SummaryEpidemiological studies indicate that the consumption of soy-containing food may prevent or slow-down the development of cardiovascular disease. In endothelial cells application of a soy extract or a combination of the most abundant soy isoflavones genistein and daidzein both inhibited apoptosis, a driving force in atherosclerosis development, when applied in combination with oxidized LDL or homocysteine. Proteome analysis revealed that the stressorinduced alteration of protein expression profile was reversed by the soy extract or the genistein/daidzein mixture. Only few protein entities that could be functionally linked to mitochondrial dysfunction were regulated in common by both application forms of isoflavones. A dietary intervention with isoflavone-enriched soy extract in postmenopausal women, who generally show strongly increased cardiovascular risk due to diminished estrogen production, led to significant alterations in the steady state levels of proteins from mononuclear blood cells. The proteins identified by proteome analysis revealed that soy isoflavones may increase the anti-inflammatory response in blood mononuclear cells thereby contributing to the atherosclerosispreventive activities of a soy-rich diet. Conclusion: By proteome analysis protein targets were identified in vitro in endothelial cells that respond to soy isoflavones and that may decipher molecular mechanisms through which soy products exert their protective effects in the vasculature.

Impact of Physical Activity on the Incidence of Vascular Diseases in Adults with Type 2 Diabetes Mellitus

2019 ◽  
Vol 8 ◽  
pp. 1549
Author(s):  
Babak Pezeshki ◽  
Ehsan Bahramali ◽  
Amir Ansari ◽  
Aliasghar Karimi ◽  
Mojtaba Frajam ◽  
...  
Keyword(s):  
Physical Activity ◽  
Diabetes Mellitus ◽  
Vascular Function ◽  
Vascular Diseases ◽  
Major Complication ◽  
Control Group ◽  
Case Group ◽  
Vascular Events ◽  
The Relationship

Background: Diabetes mellitus (DM) is a common metabolic disease worldwide and has many complications. The vascular events are the major complication of DM that have an important effect on mortality and disability. The physical activity (PA) enhances the vascular function by several pathways. The aim of this study was to evaluation of the relationship between PA and vascular diseases in patients with DM.Materials and Methods: This research was performed as the case-control study that was extracted from a prospective epidemiological research study in Iran (PERSIAN). The patients with type 2 DM more than six months defined as case group and the non-DM subjects in control group with ratio 1:2, and both groups were matched in the term of age and sex. The MET score was used to evaluate the level of PA and blood glucose, lipid profile, body mass index, overweight, dyslipidemia, glomerular filtration rate, myocardial infarction (MI), unstable angina, and stroke.Results: Overall, 1242 patients with DM were extracted, and 2484 non-diabetic subjects were investigated. In the case group, 355(28.6 %) and 887(71.4%) were men and women, respectively, the and 710 (28.6%) men and 1774(71.4%) women in control group. The mean MET score was 30 and 40.97 in the DM and non-DM groups, respectively (P˂0.001). The frequency of MI, stroke, and cardiac ischemia were 44 (3.5%), 37 (3%), and 267 (21.5%), respectively in DM group, and 54 (2.2%), 43 (1.7%), and 389 (15.7%), respectively in non-DM group.Conclusion: The incidence of vascular events associated with PA level in patients with DM and adherence to regular PA reduce the vascular events and DM complications. [GMJ.2019;inpress:e1549]

PENGARUH PEMBERIAN KOMBINASI EKSTRAK BUAH MENGKUDU (Morinda citrifolia L.) DAN KUNYIT (Curcuma longa) TERHADAP HISTOPATOLOGI GINJAL TIKUS WISTAR YANG DIINDUKSI ALLOXAN

2020 ◽  
Vol 5 (2) ◽  
pp. 319-327
Author(s):  
Pelastri Rahayu ◽  
◽  
Retno Hestiningsih ◽  
Martini Martini ◽  
Dwi Sutiningsih ◽  
...  
Keyword(s):  
Body Weight ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Curcuma Longa ◽  
Morinda Citrifolia ◽  
Control Group ◽  
Type I ◽  
Turmeric Extract ◽  
Measurement Results ◽  
Diabetes Nephropathy

The prevalence of DM in Riskesdas in 2018 according to the Perkeni consensus in 2015 is higher than according to the Perkeni consensus in 2011, the prevalence was10.9%. The disease can develop into diabetes nephropathy, Increased prevalence of diabetic nephropathy directly proportional with an increase in diabetes prevalence. Diabetic nephropathy is a microvascular complication in diabetics that develops around 30% in patients with type I DM and about 40% in patients with type II DM. Turmeric extract has antioxidant and anti-inflammatory effects to prevent the bad development of diabetes nephropathy. This study looked at the effect of giving a combination of noni and turmeric extract on histopathology of alloxan-induced renal rats. A total of 25 mice were divided into 5 treatment groups, namely the PI group (250 mg / kgBB extract dose), PII group (500 mg / kgBB extract dose), PIII group (750 mg / kgBB extract dose), positive control group (glibenklamid) and negative control group (without extract and glibenklamid). The study used Post Test Only Group. The highest percentage decrease in blood glucose in the PI group was 56.11% and the lowest decrease in the PIII group was 24.12% with p = 0.012. The results of the study were not based on the number of extract doses. The measurement results of rat body weight and glomerular diameter were not affected by blood glucose level with p = 0.700 for body weight and p = 0.187 for glomerular measurement results.

Withdrawn: Hepatoprotective effects of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) hydro-alcholic extract on non-alcoholic fatty liver-induced rats

2016 ◽  
Vol 3 (5) ◽  
pp. 143
Author(s):  
Fatemeh Almasi ◽  
Mozafar Khazaei ◽  
Shima Chehrei ◽  
Ali Ghanbari
Keyword(s):  
Fatty Liver ◽  
Liver Tissue ◽  
Serum Lipid ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Lipid Profiles ◽  
Control Group ◽  
Tribulus Terrestris ◽  
Protective Effects ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver induces many complications to the liver tissue and also serum related parameters. Medicinal plants are the safe therapeutic strategy for the treatment of diseases. In this regards, the present study was conducted to evaluate the effect of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) extract on non-alcoholic fatty liver in rats. In this experimental study, thirty male Wistar rats were divided into five groups (n = 6). Animals in experimental groups were received high fructose diet (70%) (HDF) daily alone or in combined with daily intraperitoneal injection of 500, 700 and 1,000 mg/kg extract of T. terrestris. Control group of rats was feed with standard chow. The serum levels of biomarkers of liver and serum lipid profiles were assessed, also histopathological examination of liver tissue done. Data were analyzed using One-way ANOVA method followed by Tukey’s post-hoc multiple comparison test and P < 0.05 was considered statistically significant. There were significant improvements for biomarkers of liver tissue (P < 0.05) and serum lipid profiles (P < 0.01) in the HFD-fed rats that were treated with T. terrestris extract compare to HFD-fed group. In addition, accumulation of lipids in hepatocytes was significantly reduced in the HFD-fed + extract administrated groups in comparison to HFD-fed rats (P < 0.01). T. terrestris extract has protective effects against non-alcoholic fatty liver by changing biomarkers of liver tissue, serum lipid profiles and histopathological anomalies of liver tissue, to normal range.

Sign in / Sign up

Export Citation Format

Share Document