scholarly journals Testosterone aggravates cerebral vascular injury by reducing plasma HDL levels

2020 ◽  
Vol 15 (1) ◽  
pp. 1042-1048
Author(s):  
Tao Jin ◽  
Lu Wang ◽  
Dongbo Li ◽  
Tao Yang ◽  
Yuefei Zhou
Keyword(s):  
Oxidative Stress ◽  
Soybean Oil ◽  
Vascular Injury ◽  
Cerebral Artery ◽  
Cell Apoptosis ◽  
Density Lipoprotein ◽  
Tnf Α ◽  
And Oxidative Stress ◽  
Cerebral Vascular

AbstractTestosterone is often used to improve the physiological function. But increased testosterone levels affect blood lipids and cause inflammation and oxidative stress, which are risk factors for vascular diseases. This study aimed at investigating the effects of testosterone on cerebral vascular injury using an established intracranial aneurysm (IA) model. Sixteen-week-old female C57Bl/6 mice were subcutaneously infused with testosterone propionate (TP; 5 mg/kg day) or plain soybean oil (controls) for 6 weeks. After 2 weeks of treatment, mice were given angiotensin II-elastase for another 4 weeks. The results showed that TP significantly increased cell apoptosis and reactive oxygen species production in cerebral artery, together with increases in plasma tumor necrosis factor-α (TNF-α) levels and in urinary 8-isoprostane levels. Plasma assays showed that 2 weeks after TP or soybean oil administration, the high-density lipoprotein (HDL) level was higher in the TP group than in controls. In vitro studies showed that testosterone increased TNF-α and monocyte chemotactic protein-1 mRNA and protein expression levels in RAW 264.7 macrophages. In summary, by reducing the HDL level, TP aggravates cerebral artery injury by increasing cell apoptosis, inflammation, and oxidative stress.

Etanercept Improves Lipid Profile and Oxidative Stress Measures in Patients with Juvenile Idiopathic Arthritis

2013 ◽  
Vol 40 (6) ◽  
pp. 943-948 ◽  
Author(s):  
Sara De Sanctis ◽  
M. Loredana Marcovecchio ◽  
Stefania Gaspari ◽  
Marianna Del Torto ◽  
Angelika Mohn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Lipid Profile ◽  
Proinflammatory Cytokines ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Oxidative Stress Marker ◽  
Tnf Α ◽  
And Oxidative Stress

Objective.To investigate the effect of 1-year treatment with the anti-tumor necrosis factor-α (TNF-α) drug etanercept on lipid profile and oxidative stress in children and adolescents with juvenile idiopathic arthritis (JIA).Methods.Thirty children with JIA (22 females; mean age 12.3 ± SD 5.7 yrs), all eligible for anti-TNF-α treatment, were assessed at baseline and after 6- and 12-month treatment with etanercept. Disease activity was determined using the Juvenile Arthritis Disease Activity Score (JADAS). Blood samples were drawn to measure the acute-phase reactants C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), lipids, and the proinflammatory cytokines TNF-α, interleukin-1β (IL-1β), IL-6 and interferon-γ. To measure the oxidative stress marker 8-iso-prostaglandin F2α, 24-h urine samples were collected.Results.Inflammatory indicators (CRP and ESR) and JADAS scores improved significantly after 1 year of etanercept treatment (all p < 0.001). Proinflammatory cytokines showed significant reduction during the study period (all p < 0.001). Similar reductions were detected in total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p = 0.04), and triglycerides (p < 0.001), whereas no significant change was found in high-density lipoprotein cholesterol. No side effects were observed during the treatment period.Conclusion.This study shows for the first time that anti-TNF-α therapy for JIA is associated not only with a beneficial effect on clinical disease activity and inflammatory indexes, but also with improved lipid profile and oxidative stress. These findings suggest that TNF-α blockers might reduce atherosclerotic risk in children with JIA.

scholarly journals Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Huanjin Song ◽  
Hao Wu ◽  
Jun Dong ◽  
Sihua Huang ◽  
Jintao Ye ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Ellagic Acid ◽  
Oxidative Stress Marker ◽  
Dependent Manner ◽  
Histone Deacetylase 1 ◽  
Protein Levels ◽  
Tnf Α ◽  
And Oxidative Stress

Ellagic acid (EA) was reported to play protective roles in rheumatoid arthritis (RA). It was found that the level of metastasis-associated gene 1 (MTA1)/histone deacetylase 1 (HDAC1) protein complex was downregulated by polyphenols in several human disorders. Notably, inhibition of MTA1 or HDAC1 has anti-inflammatory effects on RA. Therefore, our study is aimed at investigating whether EA prevents RA progression through regulating the MTA1/HDAC1 complex. Herein, the human fibroblast-like synoviocyte (FLS) cell line MH7A was treated with TNF-α to induce an inflammation model in vitro and then incubated with different concentrations of EA. Western blot analysis showed that EA reduced MTA1 expression in a dose-dependent manner in MH7A cells. Then, TNF-α-treated MH7A cells were incubated with EA alone or together with MTA1 overexpression plasmid (pcDNA-MTA1), and we found that EA inhibited proliferation, inflammation cytokine levels, and oxidative stress marker protein levels and promoted apoptosis in MH7A cells, while MTA1 overexpression abolished these effects. Moreover, coimmunoprecipitation assay verified the interaction between MTA1 and HDAC1. EA downregulated the MTA1/HDAC1 complex in MH7A cells. MTA1 knockdown inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells, while HDAC1 overexpression reversed these effects. Moreover, chromatin immunoprecipitation assay indicated that EA inhibited HDAC1-mediated Nur77 deacetylation. Rescue experiments demonstrated that Nur77 knockdown reversed the effects of EA on MH7A cell biological behaviors. Additionally, EA treatment attenuated arthritis index, paw swelling, synovial hyperplasia, and inflammation in collagen-induced arthritis (CIA) rats. In conclusion, EA inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells and alleviated the severity of RA in CIA rats though downregulating MTA1/HDAC1 complex and promoting HDAC1 deacetylation-mediated Nur77 expression.

scholarly journals Resveratrol Suppresses Annulus Fibrosus Cell Apoptosis through Regulating Oxidative Stress Reaction in an Inflammatory Environment

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Qunqun Shan ◽  
Ning Li ◽  
Fan Zhang ◽  
Peng Yu ◽  
Qingxi Meng
Keyword(s):  
Oxidative Stress ◽  
Disc Degeneration ◽  
Cell Apoptosis ◽  
Annulus Fibrosus ◽  
Caspase 3 ◽  
Stress Reaction ◽  
Sod Activity ◽  
Tnf Α ◽  
Apoptosis Ratio

During disc degeneration, the increase of inflammatory cytokines and decrease of disc cell density are two prominent features. Enhanced inflammatory reaction contributes to disc annulus fibrosus (AF) cell apoptosis. In this study, we investigated whether resveratrol can suppress AF cell apoptosis in an inflammatory environment. Rat disc AF cells were cultured in medium with or without tumor necrosis factor-α (TNF-α). Resveratrol was added along with the culture medium supplemented with TNF-α. Caspase-3 activity, cell apoptosis ratio, expression of apoptosis-associated molecules (Bcl-2, Bax, caspase-3, cleaved PARP, and cleaved caspase-3), reactive oxygen species (ROS) content, and the total superoxide dismutase (SOD) activity were measured. Our results showed that TNF-α significantly increased caspase-3 activity and AF cell apoptosis ratio and upregulated gene/protein expression of Bax, caspase-3, cleaved caspase-3, and cleaved PARP, whereas it downregulated the expression of Bcl-2. Moreover, TNF-α significantly increased ROS content but decreased the total SOD activity. Further analysis demonstrated that resveratrol partly attenuated the effects of TNF-α on AF cell apoptosis-associated parameters, decreased ROS content, and increased the total SOD activity in the AF cells treated with TNF-α. In conclusion, resveratrol attenuates inflammatory cytokine TNF-α-induced AF cell apoptosis through regulating oxidative stress reaction in vitro. This study sheds a new light on the protective role of resveratrol in alleviating disc degeneration.

scholarly journals Compound Dragon’s blood capsule alleviates the degree of myocardial ischemia by improving inflammation and oxidative stress

2022 ◽  
Author(s):  
Xinkai Lyu ◽  
Xinyue Chang ◽  
Xiao Mi ◽  
Meigeng Hu ◽  
Yue Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Colorimetric Method ◽  
New Drugs ◽  
H9c2 Cell ◽  
Dragon’S Blood ◽  
Tnf Α ◽  
And Oxidative Stress

Abstract Background: Compound Dragon's blood capsule (CDC) is a patent medicine mainly composed of dragon’s blood (Dracaena cochinchinensis (Lour.) S. C. Chen), notoginseng (Parmx notoginseng (Burk.) F. H. Chen) and borneol (C10H18O) for the treatment of stabilize coronary heart disease (CHD) and myocardial ischemia (MI). This paper is to investigate the anti-myocardial ischemia properties of CDC both in vivo and vitro.Methods: The fingerprint of CDC was established by UPLC-Q/TOF-MS. The hypoxia/reoxygenation (H/R) model was established by using H9c2 cells. The levels of LDH, SOD and MDA were detected by colorimetric method. Moreover, the MI model of rats was established by isoprenaline hydrochloride (ISO), the mortality rate was recorded, the changes in J point of electrocardiogram were determined, the expressions of the myocardial markers, oxidative stress markers (CK, CK-MB, LDH and SOD) and inflammatory mediators (TNF-α, IL-6, IL-10, IL-1β and NO) in serum were detected. Results: The fingerprint of CDC was established and 10 mainly active components were identified: 7,4'-dihydroxyflavone, resveratrol, loureirin A, loureirin B, pterostilbene were identified from Dragon's blood, notoginsenoside R1, ginsenoside Rg1, ginsenoside Rb1, oleanolic acid, ginsenoside Rd were identified from notoginseng. In vitro study, CDC significantly improved H9c2 cell viability and SOD level (P < 0.05), decreased LDH and MDA level (P < 0.05). In vivo study, CDC increased survival rate and SOD level of serum, decreased J-point of ECG, CK-MB, LDH, TNF-α, IL-6, IL-10 level (P < 0.05).Conclusions: CDC had a significant anti-myocardial ischemia effect by alleviating inflammation and oxidative stress, suggesting that CDC is a suitable adjuvent to treat CHD, dragon’s blood has the prospect of developing other new drugs.

scholarly journals Cardioprotective Roles of β-Hydroxybutyrate Against Doxorubicin Induced Cardiotoxicity

2021 ◽  
Vol 11 ◽  
Author(s):  
Yihai Liu ◽  
Xuan Wei ◽  
Mingyue Wu ◽  
Jiamin Xu ◽  
Biao Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Cell Apoptosis ◽  
Mitochondrial Membrane ◽  
Membrane Integrity ◽  
Reverse Remodeling ◽  
Acid Oxidation ◽  
Doxorubicin Group ◽  
And Oxidative Stress

Background: β-Hydroxybutyrate (BHB) is produced by fatty acid oxidation in the liver under the fasting state and confirmed to play a cardioprotective role in ischemia and hypertensive settings. Doxorubicin (DOX) is an effective chemotherapeutic drug, but limited by serious irreversible cardiotoxicity. However, whether BHB can protect from DOX-induced cardiotoxicity remains unknown.Methods and Results: C57BL/6 mice were intraperitoneally injected with DOX to induce cardiac toxicity and intragastrically administered into BHB for treatment. They were randomly divided into three groups, namely a sham group (Sham), a doxorubicin group (DOX), and a doxorubicin+β-Hydroxybutyrate group (DOX + BHB). Echocardiography and pathological staining were performed to evaluate cardiac function and fibrosis. H9c2 cardiomyocyte was treated with DOX or BHB for in vitro experiments. Cell apoptosis and ROS were determined by flow cytometry. BHB significantly restored DOX-induced cardiac function decline and partially prevented cardiac reverse remodeling, characterized by increased cell size and decreased fibrosis. In vitro, BHB treatment decreased cellular injury and apoptosis. Also, BHB alleviated oxidative stress level and increased mitochondrial membrane potential.Conclusion: Our results suggested that BHB could protected from DOX-induced cardiotoxicity by inhibiting cell apoptosis and oxidative stress and maintaining mitochondrial membrane integrity.

scholarly journals Mitochondrial-Targeting Antioxidant SS-31 Suppresses Airway Inflammation and Oxidative Stress Induced by Cigarette Smoke

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
De-qing Yang ◽  
Qiu-nan Zuo ◽  
Tao Wang ◽  
Dan Xu ◽  
Liu Lian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Airway Inflammation ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Mapk Signaling ◽  
Tnf Α ◽  
And Oxidative Stress

This study investigated whether the mitochondrial-targeted peptide SS-31 can protect against cigarette smoke- (CS-) induced airway inflammation and oxidative stress in vitro and in vivo. Mice were exposed to CS for 4 weeks to establish a CS-induced airway inflammation model, and those in the experimental group were pretreated with SS-31 1 h before CS exposure. Pathologic changes and oxidative stress in lung tissue, inflammatory cell counts, and proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. The mechanistic basis for the effects of SS-31 on CS extract- (CSE-) induced airway inflammation and oxidative stress was investigated using BEAS-2B bronchial epithelial cells and by RNA sequencing and western blot analysis of lung tissues. SS-31 attenuated CS-induced inflammatory injury of the airway and reduced total cell, neutrophil, and macrophage counts and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, and matrix metalloproteinase (MMP) 9 levels in BALF. SS-31 also attenuated CS-induced oxidative stress by decreasing malondialdehyde (MDA) and myeloperoxidase (MPO) activities and increasing that of superoxide dismutase (SOD). It also reversed CS-induced changes in the expression of mitochondrial fission protein (MFF) and optic atrophy (OPA) 1 and reduced the amount of cytochrome c released into the cytosol. Pretreatment with SS-31 normalized TNF-α, IL-6, and MMP9 expression, MDA and SOD activities, and ROS generation in CSE-treated BEAS-2B cells and reversed the changes in MFF and OPA1 expression. RNA sequencing and western blot analysis showed that SS-31 inhibited CS-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway in vitro and in vivo. Thus, SS-31 alleviates CS-induced airway inflammation and oxidative stress via modulation of mitochondrial function and regulation of MAPK signaling and thus has therapeutic potential for the treatment of airway disorders caused by smoking.

scholarly journals CFTR improves myocardial ischemic/reperfusion injury through activating FUNDC1-mediated mitophagy and regulating ATP and mitochondrial functions

2020 ◽  
Author(s):  
Yaping Zhang ◽  
Nan Ding ◽  
Hanlu Yi ◽  
Yudong Zhao ◽  
Daole Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Protein Levels ◽  
Ischemic Reperfusion ◽  
Atp Concentration ◽  
Mitochondrial Functions ◽  
Tnf Α ◽  
Apoptosis Related Protein ◽  
Related Proteins

Abstract Background To investigate the potential role of CFTR in myocardial ischemic/reperfusion (I/R) injury and its relationship with mitophagy. Methods Wild type (WT) and age matched CFTR−/− male mice were used to establish the myocardial I/R model. CFTR activator forskolin (FSK) was used to activate CFTR in mice. Hypoxia/reoxygenation (H/R) treatment was used for in vitro model in WT or CFTR−/− cardiomyocytes. The autophagy inhibitor 3-MA and activator rapamycin was used for inhibition or activation of autophagy, respectively. The mitochondrial membrane potential (MMP) and ATP concentration were detected. Immunofluorescence was performed for measurement of mitochondria. Oxidative factors reactive oxygen species (ROS), superoxide dismutase (SOD), malondiadehycle (MDA) and glutathione peroxidase (GSH-PX) were detected. The expression of CFTR, MMP-9, TNF-α, IL-8, LC3 II/I, beclin1, caspase-3, caspase-8, caspase-9, bax, bcl-2, p-62 and FUNDC1 was determined using western blotting or PCR. Results Knockdown of CFTR significantly increased the infraction volume and decreased the expression of autophagy related proteins beclin1 and LC3II/I in mice. In H/R cardiomyocytes, deficiency of CFTR by induced dysfunction of mitochondrial, decrease of ATP concentration and enhanced oxidative stress, as well as inhibited mitophagy and increased cell apoptosis related protein levels. When treated with 3-MA, the effects of overexpression of CFTR was remarkably reversed, while treatment of rapamycin significantly reversed the effects of inhibiting CFTR on both mitophagy, oxidative stress and cell apoptosis related proteins. The inhibition of FUNDC1 also reversed the above effects of overexpressing CFTR. Conclusion Inhibition of CFTR could promote myocardial I/R injury by suppressing FUNDC1-mediated mitophagy and activating of oxidative stress.

Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

2020 ◽  
Vol 25 (40) ◽  
pp. 4310-4317 ◽  
Author(s):  
Lichao Sun ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Oxidative Stress ◽  
Brain Edema ◽  
Severity Score ◽  
Global Ischemia ◽  
Signal Pathways ◽  
Neurological Severity Score ◽  
Tnf Α ◽  
Transient Global Ischemia ◽  
And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

scholarly journals Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo
Keyword(s):  
Oxidative Stress ◽  
Food Sources ◽  
Preventive Action ◽  
Nutritional Interventions ◽  
Beneficial Effects ◽  
Age Related ◽  
Macromolecular Damage ◽  
And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

Neuroprotection of chromobox 7 knockout in the mouse after cerebral ischemia-reperfusion injury via nuclear factor E2-related factor 2/hemeoxygenase-1 signaling pathway

2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Water Content ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cerebral Ischemia Reperfusion ◽  
And Oxidative Stress

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

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