scholarly journals Triptolide regulates oxidative stress and inflammation leading to hepatotoxicity via inducing CYP2E1

2021 ◽  
pp. 096032712110563
Author(s):  
Hai-Yan Jiang ◽  
Yan-Ni Bao ◽  
Feng-Mei Lin ◽  
Yong Jin
Keyword(s):  
Oxidative Stress ◽  
Opposite Effect ◽  
Enzyme Inhibitor ◽  
Signal Pathway ◽  
Activation Mechanism ◽  
Control Group ◽  
Tripterygium Wilfordii Hook F ◽  
Tripterygium Wilfordii Hook

Triptolide (TP), the main active compound extracted from medicine— tripterygium wilfordii Hook f. (TWHF). It has anti-tumor and immunomodulatory properties. Our study aimed to investigate the mechanisms of hepatotoxicity treated with TP in vivo and in vitro, as well as their relationship with the NF-κB (p65) signal pathway; and to assess TP-induced hepatotoxicity after CYP2E1 modulation by the known inhibitor, clomethiazole, and the known inducer, pyrazole. Mice were given TP to cause liver injury and IHHA-1 cells were given TP to cause hepatocyte injury. The enzyme activity and hepatotoxicity changed dramatically when the CYP2E1 inhibitor and inducer were added. In comparison to the control group, the enzyme inducer increased the activity of CYP2E1, whereas the enzyme inhibitor had the opposite effect. Our findings suggest that TP is an inducer of CYP2E1 via a time-dependent activation mechanism. In addition, TP can promote oxidative stress, inflammatory and involving the NF-κB (p65) signal pathway. Therefore, we used triptolide to stimulate C57 mice and IHHA-1 cells to determine whether TP can promote oxidative stress and inflammation by activating CYP2E1 in response to exacerbated liver damage and participate in NF-κB (p65) signaling pathway.

scholarly journals Arctiin Antagonizes Triptolide-Induced Hepatotoxicity via Activation of Nrf2 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yuyan Zhou ◽  
Li Xia ◽  
Weiqiang Yao ◽  
Jun Han ◽  
Guodong Wang
Keyword(s):  
Oxidative Stress ◽  
Protective Role ◽  
Protective Agent ◽  
In Vivo Models ◽  
Nrf2 Pathway ◽  
Tripterygium Wilfordii Hook F ◽  
Oxidative Stress Pathway ◽  
Tripterygium Wilfordii Hook

Triptolide (TP) is the most effective ingredient found in the traditional Chinese herbal Tripterygium wilfordii Hook F, and it is widely used in therapies of autoimmune and inflammatory disorders. However, the hepatotoxicity induced by TP has restricted its use in clinical trials. Arctiin is known as a protective agent against oxidative stress, and it exerts liver-protecting effect. This study was aimed at investigating the protective role of arctiin against TP-induced hepatotoxicity using in vitro and in vivo models. The results indicated that TP not only obviously induced liver injury in mice but also significantly inhibited the growth of HepG2 cells and increased the level of intracellular reactive oxygen. Furthermore, TP obviously decreased the expressions of proteins of Nrf2 pathway including HO-1, NQO1, and Nrf2 associated with oxidative stress pathway. However, the above experimental indexes were reversed by the treatment of arctiin. Our results suggested that arctiin could alleviate TP-induced hepatotoxicity, and the molecular mechanism is likely related to its capacity against oxidative stress.

scholarly journals Assemble Flavone of Rhizoma Drynariae Promotes Differentiation of Osteoblasts and Growth of Bone Graft in Induced Membrane Partly by Activating Wnt/β-Catenin Signal Pathway

2020 ◽  
Author(s):  
Shuyuan Li ◽  
Hongliang zhou ◽  
Chenghu Hu ◽  
Jiabao Yang ◽  
Yue Li ◽  
...  
Keyword(s):  
Bone Graft ◽  
Signal Pathway ◽  
Autogenous Bone ◽  
Control Group ◽  
Sprague Dawley ◽  
Induced Membrane ◽  
Membrane Technique ◽  
Rhizoma Drynariae

Abstract Background: Assemble Flavone of Rhizoma Drynariae (AFRD) is not only the extract of Rhizoma Drynariae, but also the effective component of Qianggu capsule, which is widely used in the treatment of fracture, bone defect, osteoporosis and other orthopedic diseases, and has achieved good results. Purpose of this trial was to explore effects of AFRD on bone graft mineralization and osteoblast differentiation in Masquelet induced membrane in rats.Methods: Twenty male Sprague-Dawley rats aged 10-12 weeks were randomLy divided into AFRD group (n=10) and control group (n=10). Critical-sized defects model of rats was established with 10 rats in each group. Polymethyl methacrylate (PMMA) was implanted into the defect of femur in rats. After the formation of the induced membrane, autogenous bone was implanted into the induced membrane. After 10 weeks of bone grafting, bone tissue in the bone graft area was examined by X-ray, Micro-CT and hematoxylin-eosin (HE) staining to evaluate the growth of the bone graft. Serums of the two groups of rats were extracted respectively, and these serums were used to culture osteoblasts in vitro. CKK8 method, Alkaline phosphatase (ALP) staining, Western blot and RT-PCR and other methods were used to evaluate the effects of AFRD on the proliferation of osteoblasts and the regulation of Wnt/β-catenin signal pathway.Results: In vivo experiment showed that the growth and mineralization effect of bone graft in AFRD group was better. In vitro experiment showed that osteoblasts proliferated faster, ALP activity was higher, number of mineralized nodules was more, and expression of proteins related to Wnt/β-catenin signal pathway and osteogenesis were more in AFRD group.Conclusions: AFRD can promote mineralization of bone graft and differentiation of osteoblasts during the bone graft growth period of induced membrane technique, which is related to the activation of Wnt/ β-catenin signal pathway.

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 Novel PGC-1α/ATF5 Axis Partly Activates UPRmt and Mediates Cardioprotective Role of Tetrahydrocurcumin in Pathological Cardiac Hypertrophy

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Bing Zhang ◽  
Yanzhen Tan ◽  
Zhengbin Zhang ◽  
Pan Feng ◽  
Wenyuan Ding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Hypertrophy ◽  
Test Group ◽  
Neonatal Rat ◽  
Activation Mechanism ◽  
Cardiomyocyte Hypertrophy ◽  
Control Group ◽  
Pathological Cardiac Hypertrophy

Mitochondrial unfolding protein response (UPRmt) effectively resists the pathological cardiac hypertrophy and improves the mitochondrial function. However, the specific activation mechanism and drugs that can effectively activate UPRmt in the cardiac muscle are yet to be elucidated. The aim of this study was to determine the regulation role of UPRmt on preventing pathological cardiac hypertrophy by tetrahydrocurcumin (THC) and explore its underlying molecular mechanism. Male C57BL/6J wild-type (WT) mice were divided into a control group and subjected to sham treatment for 4 weeks, and a test group which was subjected to transverse aortic constriction (TAC) surgery. Animals in the control and test group were orally administered THC (50 mg/kg) for 4 weeks after TAC procedure; an equivalent amount of saline was orally administered in the control sham-treated group and the TAC group. Subsequently, oxidative stress and UPRmt markers were assessed in these mice, and cardiac hypertrophy, fibrosis, and cardiac function were tested. Small interfering RNA (siRNA) targeting proliferator-activated receptor-gamma coactivator (PGC)-1α and activating transcription factor 5 (ATF5) were used to determine the UPRmt activation mechanism. THC supplement partly upregulated UPRmt effectors and inhibited TAC-induced oxidative stress compared with TAC-operated WT mice, thereby substantially attenuating contractile dysfunction, cardiac hypertrophy, and fibrosis. Furthermore, PGC-1α knockdown blunted the UPRmt activation and the cardioprotective role of THC. The interaction between PGC-1α and ATF5 was tested in neonatal rat cardiac myocytes under normal conditions. The results showed that PGC-1α was an upstream effector of ATF5 and partly activated UPRmt. In vitro, phenylephrine- (PE-) induced cardiomyocyte hypertrophy caused ATF5 upregulating rather than downregulating corresponding to the downregulation of PGC-1α. The PGC-1α/ATF5 axis mediated the UPRmt activation and stress-resistance role of THC in vitro. Collectively, the present study provides the first evidence that PGC-1 and ATF5 can form a signaling axis to partly activate UPRmt that mediates the cardioprotective role of THC in pathological cardiac hypertrophy.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document