scholarly journals Erythrocyte Fraction in Thrombi Is Increased with Serum Iron by Influencing Fibrin Networks via Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Mingli Liu ◽  
Minghui Chen ◽  
Zhongfei Hao ◽  
Qingbin Li ◽  
Yan Feng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Serum Iron ◽  
Iron Concentration ◽  
Clinical Samples ◽  
Control Group ◽  
Serum Iron Concentration ◽  
Fibrin Networks ◽  
Stroke Center

Objective. This study investigated whether the erythrocyte fraction in thrombi would be increased with serum iron via oxidative stress. Methods. This study retrospectively enrolled patients with acute ischemic stroke treated using endovascular treatment in a single stroke center from October to December 2019. We examined the relationship between serum iron and erythrocyte-rich thrombi and the correlation of serum iron and the erythrocyte fraction in thrombi using clinical samples. Experiments in vivo and in vitro were performed to investigate the influence of oxidative stress on the correlation between serum iron concentration and erythrocyte fraction in thrombi. Results. We found from the clinical samples that serum iron concentration was related to erythrocyte-rich thrombi and positively associated with the erythrocyte fraction in thrombi in vivo. Further, the tightness of the fibrin networks regulating the erythrocyte fraction in thrombi was increased with serum iron concentration in vivo. Additionally, the oxidative stress level was increased with serum iron concentration in vivo. Moreover, we found that the tightness of the fibrin networks increased with higher oxidative stress levels in vitro. Lastly, experiments in vivo with inhibiting oxidative stress showed that the erythrocyte fraction in thrombi and the tightness of fibrin networks significantly increased in the iron group than those in the iron with oxidative stress inhibitor group and control group. Conclusions. Oxidative stress played a role in the process that the erythrocyte fraction in thrombi was increased with serum iron by influencing fibrin networks.

scholarly journals The E3 Ubiquitin Ligase NEDD4-1 Mediates Temozolomide-Resistant Glioblastoma through PTEN Attenuation and Redox Imbalance in Nrf2–HO-1 Axis

2021 ◽  
Vol 22 (19) ◽  
pp. 10247
Author(s):  
Hao-Yu Chuang ◽  
Li-Yun Hsu ◽  
Chih-Ming Pan ◽  
Narpati Wesa Pikatan ◽  
Vijesh Kumar Yadav ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Biological Effects ◽  
Critical Role ◽  
Clinical Samples ◽  
Redox Imbalance ◽  
Signaling Axis ◽  
Resistant Cells

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. It is highly resistant to chemotherapy, and tumor recurrence is common. Neuronal precursor cell-expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ligase that controls embryonic development and animal growth. NEDD4-1 regulates the tumor suppressor phosphatase and tensin homolog (PTEN), one of the major regulators of the PI3K/AKT/mTOR signaling axis, as well as the response to oxidative stress. Methods: The expression levels of NEDD4-1 in GBM tissues and different cell lines were determined by quantitative real-time polymerase chain reaction and immunohistochemistry. In vitro and in vivo assays were performed to explore the biological effects of NEDD4-1 on GBM cells. Temozolomide (TMZ)-resistant U87MG and U251 cell lines were specifically established to determine NEDD4-1 upregulation and its effects on the tumorigenicity of GBM cells. Subsequently, miRNA expression in TMZ-resistant cell lines was investigated to determine the dysregulated miRNA underlying the overexpression of NEDD4-1. Indole-3-carbinol (I3C) was used to inhibit NEDD4-1 activity, and its effect on chemoresistance to TMZ was verified. Results: NEDD4-1 was significantly overexpressed in the GBM and TMZ-resistant cells and clinical samples. NEDD4-1 was demonstrated to be a key oncoprotein associated with TMZ resistance, inducing oncogenicity and tumorigenesis of TMZ-resistant GBM cells compared with TMZ-responsive cells. Mechanistically, TMZ-resistant cells exhibited dysregulated expression of miR-3129-5p and miR-199b-3p, resulting in the induced NEDD4-1 mRNA-expression level. The upregulation of NEDD4-1 attenuated PTEN expression and promoted the AKT/NRF2/HO-1 oxidative stress signaling axis, which in turn conferred amplified defense against reactive oxygen species (ROS) and eventually higher resistance against TMZ treatment. The combination treatment of I3C, a known inhibitor of NEDD4-1, with TMZ resulted in a synergistic effect and re-sensitized TMZ-resistant tumor cells both in vitro and in vivo. Conclusions: These findings demonstrate the critical role of NEDD4-1 in regulating the redox imbalance in TMZ-resistant GBM cells via the degradation of PTEN and the upregulation of the AKT/NRF2/HO-1 signaling pathway. Targeting this regulatory axis may help eliminate TMZ-resistant glioblastoma.

scholarly journals Orosomucoid 1 Attenuates Doxorubicin-Induced Oxidative Stress and Apoptosis in Cardiomyocytes via Nrf2 Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xiaoli Cheng ◽  
Dan Liu ◽  
Ruinan Xing ◽  
Haixu Song ◽  
Xiaoxiang Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Acute Phase Protein ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
H9c2 Cells ◽  
Phase Protein ◽  
New Treatment

Doxorubicin (DOX) is an effective anticancer drug, but its therapeutic use is limited by its cardiotoxicity. The principal mechanisms of DOX-induced cardiotoxicity are oxidative stress and apoptosis in cardiomyocytes. Orosomucoid 1 (ORM1), an acute-phase protein, plays important roles in inflammation and ischemic stroke; however, the roles and mechanisms of ORM1 in DOX-induced cardiotoxicity remain unknown. Therefore, in the present study, we aimed to investigate the function of ORM1 in cardiomyocytes experiencing DOX-induced oxidative stress and apoptosis. A DOX-induced cardiotoxicity animal model was established in C57BL/6 mice by administering an intraperitoneal injection of DOX (20 mg/kg), and the control group was intraperitoneally injected with the same volume of sterilized saline. The effects were assessed after 7 d. Additionally, H9c2 cells were stimulated with DOX (10 μM) for 24 h. The results showed decreased ORM1 and increased oxidative stress and apoptosis after DOX stimulation in vivo and in vitro. ORM1 overexpression significantly reduced DOX-induced oxidative stress and apoptosis in H9c2 cells. ORM1 significantly increased the expression of nuclear factor-like 2 (Nrf2) and its downstream protein heme oxygenase 1 (HO-1) and reduced the expression of the lipid peroxidation end product 4-hydroxynonenal (4-HNE) and the level of cleaved caspase-3. In addition, Nrf2 silencing reversed the effects of ORM1 on DOX-induced oxidative stress and apoptosis in cardiomyocytes. In conclusion, ORM1 inhibited DOX-induced oxidative stress and apoptosis in cardiomyocytes by regulating the Nrf2/HO-1 pathway, which might provide a new treatment strategy for DOX-induced cardiotoxicity.

scholarly journals Sulforaphane Attenuates Contrast-Induced Nephropathy in Rats via Nrf2/HO-1 Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Zhihong Zhao ◽  
Guixiang Liao ◽  
Qin Zhou ◽  
Daoyuan Lv ◽  
Harry Holthfer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Model ◽  
Renal Tissue ◽  
Antioxidant Defenses ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Contrast Induced Nephropathy ◽  
Hk2 Cells

Background. Oxidative stress plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of this study was to investigate the antioxidant effects of sulforaphane (SFN) in a rat model of CIN and a cell model of oxidative stress in HK2 cells.Methods. Rats were randomized into four groups (n=6per group): control group, Ioversol group (Ioversol-induced CIN), Ioversol + SFN group (CIN rats pretreated with SFN), and SFN group (rats treated with SFN). Renal function tests, malondialdehyde (MDA), and reactive oxygen species (ROS) were measured. Western blot, real-time polymerase chain reaction analysis, and immunohistochemical analysis were performed for nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1) detection.Results. Serum blood urea nitrogen (BUN), creatinine, and renal tissue MDA were increased after contrast exposure. Serum BUN, creatinine, and renal tissue MDA were decreased in the Ioversol + SFN group as compared with those in the Ioversol group. SFN increased the expression of Nrf2 and HO-1 in CIN rats and in Ioversol-induced injury HK2 cells. SFN increased cell viability and attenuated ROS level in vitro.Conclusions. SFN attenuates experimental CIN in vitro and in vivo. This effect is suggested to activate the Nrf2 antioxidant defenses pathway.

scholarly journals In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shintaro Mukohara ◽  
Yutaka Mifune ◽  
Atsuyuki Inui ◽  
Hanako Nishimoto ◽  
Takashi Kurosawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Matrix Metalloproteinase ◽  
Protein Expression ◽  
Achilles Tendon ◽  
Mrna Expression ◽  
High Glucose ◽  
Control Group ◽  
Type I

Abstract Background Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group. Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.

scholarly journals Endometriosis Susceptibility to Dapsone-Hydroxylamine-Induced Alterations Can Be Prevented by Licorice Intake: In Vivo and In Vitro Study

2021 ◽  
Vol 22 (16) ◽  
pp. 8476
Author(s):  
Chiara Sabbadin ◽  
Alessandra Andrisani ◽  
Gabriella Donà ◽  
Elena Tibaldi ◽  
Anna Maria Brunati ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Vitro Study ◽  
Carbonic Anhydrase Activity ◽  
Control Group ◽  
Beneficial Effects ◽  
Licorice Extract ◽  
Anti Oxidant ◽  
Gynecological Disease

Endometriosis, an estrogen-dependent chronic gynecological disease, is characterized by a systemic inflammation that affects circulating red blood cells (RBC), by reducing anti-oxidant defenses. The aim of this study was to investigate the potential beneficial effects of licorice intake to protect RBCs from dapsone hydroxylamine (DDS-NHOH), a harmful metabolite of dapsone, commonly used in the treatment of many diseases. A control group (CG, n = 12) and a patient group (PG, n = 18) were treated with licorice extract (25 mg/day), for a week. Blood samples before (T0) and after (T1) treatment were analyzed for: i) band 3 tyrosine phosphorylation and high molecular weight aggregates; and ii) glutathionylation and carbonic anhydrase activity, in the presence or absence of adjunctive oxidative stress induced by DDS-NHOH. Results were correlated with plasma glycyrrhetinic acid (GA) concentrations, measured by HPLC–MS. Results showed that licorice intake decreased the level of DDS-NHOH-related oxidative alterations in RBCs, and the reduction was directly correlated with plasma GA concentration. In conclusion, in PG, the inability to counteract oxidative stress is a serious concern in the evaluation of therapeutic approaches. GA, by protecting RBC from oxidative assault, as in dapsone therapy, might be considered as a new potential tool for preventing further switching into severe endometriosis.

scholarly journals In Vitro and in Vivo Tenocyte-protective Effectiveness of Dehydroepiandrosterone Against High Glucose-induced Oxidative Stress

2021 ◽  
Author(s):  
Shintaro Mukohara ◽  
Yutaka Mifune ◽  
Atsuyuki Inui ◽  
Hanako Nishimoto ◽  
Takashi Kurosawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Matrix Metalloproteinase ◽  
Protein Expression ◽  
Achilles Tendon ◽  
Mrna Expression ◽  
High Glucose ◽  
Control Group ◽  
Type I

Abstract BackgroundDehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. The aim of this study was to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods In an in vitro study, tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. In the in vivo study, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower, while type I collagen expression was significantly lower in the DHEA group.Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover which are affected by hyperglycemic conditions. DHEA could be a preventive drug for the diabetic tendinopathy.

scholarly journals Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts

2012 ◽  
Vol 302 (9) ◽  
pp. E1142-E1152 ◽  
Author(s):  
Baosheng Chen ◽  
Methodius G. Tuuli ◽  
Mark S. Longtine ◽  
Joong Sik Shin ◽  
Russell Lawrence ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Human Placenta ◽  
Apple Juice ◽  
Kinase Inhibitor ◽  
Pomegranate Juice ◽  
Control Group ◽  
Induced Apoptosis

The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus.

Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 997-1004 ◽  
Author(s):  
Maura Poli ◽  
Domenico Girelli ◽  
Natascia Campostrini ◽  
Federica Maccarinelli ◽  
Dario Finazzi ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Serum Iron ◽  
Iron Homeostasis ◽  
Iron Concentration ◽  
Deficiency Anemia ◽  
Hepcidin Expression ◽  
Vein Thrombosis ◽  
Protein Levels

Abstract Hepcidin is a major regulator of iron homeostasis, and its expression in liver is regulated by iron, inflammation, and erythropoietic activity with mechanisms that involve bone morphogenetic proteins (BMPs) binding their receptors and coreceptors. Here we show that exogenous heparin strongly inhibited hepcidin expression in hepatic HepG2 cells at pharmacologic concentrations, with a mechanism that probably involves bone morphogenetic protein 6 sequestering and the blocking of SMAD signaling. Treatment of mice with pharmacologic doses of heparin inhibited liver hepcidin mRNA expression and SMAD phosphorylation, reduced spleen iron concentration, and increased serum iron. Moreover, we observed a strong reduction of serum hepcidin in 5 patients treated with heparin to prevent deep vein thrombosis, which was accompanied by an increase of serum iron and a reduction of C-reactive protein levels. The data show an unrecognized role for heparin in regulating iron homeostasis and indicate novel approaches to the treatment of iron-restricted iron deficiency anemia.

Radiocontrast-induced nephropathy is attenuated by autophagy through regulation of apoptosis and inflammation

2015 ◽  
Vol 35 (7) ◽  
pp. 724-736 ◽  
Author(s):  
Gang Jee Ko ◽  
So Yeon Bae ◽  
Yu-Ah Hong ◽  
Heui Jung Pyo ◽  
Young Joo Kwon
Keyword(s):  
Oxidative Stress ◽  
Cellular Damage ◽  
Control Group ◽  
Tubular Injury ◽  
Number Of Patients ◽  
Apoptosis And Inflammation ◽  
Autophagy Inhibition

Radiocontrast-induced nephropathy (RCN) is the third most common cause of acute renal failure among inpatients. Although the number of patients undergoing exams using radiocontrast is increasing, little progress has been made for RCN treatment. The pathophysiology of RCN is known as tubular injury due to oxidative stress. As autophagy regulates cellular damage under stressful conditions, we investigated the role of autophagy in RCN. RCN was induced in male C57BL/6 J mice by intraperitoneal injection of iohexol, and 3-methyladenine (3-MA) was used as an autophagy inhibitor. Tubular injury caused by iohexol was also examined in vitro using rat tubular cells (NRK-52E). Increased autophagy after iohexol administration was demonstrated by the increase of light chain 3-II in the damaged kidney tubules both in vivo and in vitro. Serum creatinine and tubular injury were significantly increased at 24 h after iohexol treatment, as compared to control group. Further they worsened with autophagy inhibition by 3-MA. In vitro studies also demonstrated that decreased cell viability by iohexol was aggravated with 3-MA pretreatment. Malondialdehyde measured for oxidative stress was increased by iohexol, and it was accentuated by autophagy inhibition, which resulted in increase of cytochrome c. Apoptosis, increased by iohexol treatment, was augmented with autophagy inhibition. Macrophage infiltration and increase of monocyte chemotactic protein-1 in kidneys were induced by iohexol, and it was aggravated with autophagy inhibition. This study showed that autophagy was involved with the pathophysiology of RCN, and the role of autophagy in modulation of apoptosis, oxidative stress, and inflammatory cell infiltration was supposed as mechanisms mitigating RCN.

scholarly journals Effect of Xylocarpus granatum Bark Extract on Amelioration of Hyperglycaemia and Oxidative Stress Associated Complications in STZ-Induced Diabetic Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Swagat Kumar Das ◽  
Arpita Prusty ◽  
Dibyajyoti Samantaray ◽  
Mojeer Hasan ◽  
Srikanta Jena ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bark Extract ◽  
Control Group ◽  
Diabetic Mice ◽  
Mangrove Plant ◽  
Hplc Fingerprint ◽  
Xylocarpus Granatum ◽  
Serum Glutamate

Xylocarpus granatum is a medicinal mangrove plant, traditionally used for the treatment of diarrhoea, cholera, fever, dyslipidaemia, inflammation, etc. The present study was aimed to evaluate the in vitro antidiabetic (α-glucosidase inhibition assay) and antioxidant (ABTS scavenging and metal chelating assay) activities of ethanol, methanol, and aqueous extracts of leaves and barks of X. granatum followed by in vivo antidiabetic and antioxidant evaluation of ethanol bark extracts in streptozotocin- (STZ-) induced diabetic mice. The in vitro evaluation revealed higher α-amylase inhibition and ABTS scavenging activities in ethanol bark extracts of X. granatum (XGEB). Administration of XGEB at 100 and 200 mg/kg BW doses to STZ-induced diabetic mice resulted in significant decrease (P < 0.05) in blood glucose, triglyceride (TG), total cholesterol (TC), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transminase (SGPT), and urea levels in the serum of the extract administered groups as compared to diabetic control group. The levels of SOD, CAT, GPx, GR, and GST in liver along with LPx, SOD, GST, and GR activities in brain tissues were found to be ameliorated in XGEB treated diabetic mice. Histopathological alternations of liver tissues were also found to be restored in XGEB treated diabetic groups. The HPLC fingerprint analysis of XGEB revealed the presence of simple polyphenols, isoflavone, and flavonol-like compounds. The DSC and UV-VIS analysis also confirmed the presence of phenolic compounds in XGEB. The GC-MS analysis of XGEB showed the presence of a number of bioactive compounds. These results demonstrated the beneficial effect of XGEB in controlling hyperglycaemia and ameliorating oxidative stress associated complications associated with diabetes.

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