scholarly journals Leptin Administration Downregulates the Increased Expression Levels of Genes Related to Oxidative Stress and Inflammation in the Skeletal Muscle ofob/obMice

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Neira Sáinz ◽  
Amaia Rodríguez ◽  
Victoria Catalán ◽  
Sara Becerril ◽  
Beatriz Ramírez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Thiobarbituric Acid ◽  
Immune Defense ◽  
Low Grade ◽  
Wild Type ◽  
Expression Levels ◽  
Leptin Deficiency ◽  
Markers Of Oxidative Stress

Obese leptin-deficientob/obmice exhibit a low-grade chronic inflammation together with a low muscle mass. Our aim was to analyze the changes in muscle expression levels of genes related to oxidative stress and inflammatory responses in leptin deficiency and to identify the effect ofin vivoleptin administration.Ob/obmice were divided in three groups as follows: controlob/ob, leptin-treatedob/ob(1 mg/kg/d) and leptin pair-fedob/obmice. Gastrocnemius weight was lower in controlob/obthan in wild type mice (P<.01) exhibiting an increase after leptin treatment compared to control and pair-fed (P<.01)ob/obanimals. Thiobarbituric acid reactive substances, markers of oxidative stress, were higher in serum (P<.01) and gastrocnemius (P=.05) of controlob/obthan in wild type mice and were significantly decreased (P<.01) by leptin treatment. Leptin deficiency altered the expression of 1,546 genes, while leptin treatment modified the regulation of 1,127 genes with 86 of them being involved in oxidative stress, immune defense and inflammatory response. Leptin administration decreased the high expression ofCrybb1, Hspb3, Hspb7, Mt4, Cat, Rbm9, Serpinc1andSerpinb1aobserved in controlob/obmice, indicating that it improves inflammation and muscle loss.

scholarly journals Effects of Pirfenidone and Nintedanib on Markers of Systemic Oxidative Stress and Inflammation in Patients with Idiopathic Pulmonary Fibrosis: A Preliminary Report

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1064
Author(s):  
Alessandro G. Fois ◽  
Elisabetta Sotgiu ◽  
Valentina Scano ◽  
Silvia Negri ◽  
Sabrina Mellino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Thiobarbituric Acid ◽  
Related Factor ◽  
Beneficial Effects ◽  
Systemic Oxidative Stress ◽  
Markers Of Oxidative Stress

Introduction: In vitro evidence suggests that pirfenidone and nintedanib, approved agents for the treatment of idiopathic pulmonary fibrosis (IPF), exert anti-inflammatory and anti-oxidant effects. We aimed to investigate such effects in vivo in IPF patients. Methods: Systemic circulating markers of oxidative stress [nuclear factor erythroid 2–related factor 2 (Nrf2), thiobarbituric acid- reactive substances (TBARS), homocysteine (Hcy), cysteine (Cys), asymmetric dimethylarginine (ADMA) and ADMA/Arginine ratio, glutathione (GSH), plasma protein –SH (PSH), and taurine (Tau)] and inflammation [Kynurenine (Kyn), Tryptophan (Trp) and Kyn/Trp ratio] were measured at baseline and after 24-week treatment in 18 IPF patients (10 treated with pirfenidone and 8 with nintedanib) and in 18 age- and sex-matched healthy controls. Results: Compared to controls, IPF patients had significantly lower concentrations of reduced blood GSH (457 ± 73 µmol/L vs 880 ± 212 µmol/L, p < 0.001) and plasma PSH (4.24 ± 0.95 µmol/g prot vs 5.28 ± 1.35 µmol/g prot, p = 0.012). Pirfenidone treatment significantly decreased the Kyn/Trp ratio (0.030 ± 0.011 baseline vs 0.025 ± 0.010 post-treatment, p = 0.048) whilst nintedanib treatment significantly increased blood GSH (486 ± 70 μmol/L vs 723 ± 194 μmol/L, p = 0.006) and reduced ADMA concentrations (0.501 ± 0.094 vs. 0.468 ± 0.071 μmol/L, p = 0.024). Conclusion: pirfenidone and nintedanib exert beneficial effects on specific markers of oxidative stress and inflammation in IPF patients.

Extract of the plant Cotinus coggygria Scop. attenuates pyrogallol-induced hepatic oxidative stress in Wistar rats

2011 ◽  
Vol 89 (6) ◽  
pp. 401-411 ◽  
Author(s):  
Sanja Matić ◽  
Snežana Stanić ◽  
Desanka Bogojević ◽  
Melita Vidaković ◽  
Nevena Grdović ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Phase ◽  
Wistar Rats ◽  
Thiobarbituric Acid ◽  
Hepatoprotective Activity ◽  
Acute Phase Reactants ◽  
Markers Of Oxidative Stress ◽  
Cotinus Coggygria

To examine the protective potential of the Cotinus coggygria Scop. methanol extract, Wistar rats were treated with the hepatotoxic compound pyrogallol, which possesses a potent ability to generate free radicals and induce oxidative stress. The ability of the extract to counteract the oxidative stress was examined in rats that were injected with the extract intraperitoneally (500 mg·(kg body weight)–1) either 2 or 12 h before the pyrogallol treatment. The extract possesses a reducing activity in vitro and an ability to chelate the ferrous ion both in vivo and in vitro. Application of the extract prior to pyrogallol treatment led to a decrease in the levels of thiobarbituric acid-reactive substances, aspartate aminotransferase, and alanine aminotransferase, increased activities of antioxidant enzymes and attenuation of DNA damage, as well as increased Akt activity and inhibition of NF-κB protein expression. Treatment with the extract 12 h prior to pyrogallol administration was more effective in suppressing pyrogallol-induced oxidative damage than the 2 h pretreatment. Extract administration promoted an increase in acute phase reactants haptoglobin and α2-macroglobulin that was short of a full-fledged acute phase response. Administration of the extract considerably improved the markers of oxidative stress, thus revealing a potential hepatoprotective activity. Our results suggest that Akt activation, NF-κB inhibition, and induction of the acute phase play important roles in mediating hepatic protection by the extract. The greater effectiveness of the 12 h pretreatment with extract points to the important role that preconditioning assumes in improving resistance to subsequent exposure to oxidative stress.

scholarly journals First phytochemical and biological study of the ethanolic extract from leaves of Capirona decorticans (Rubiaceae)

2018 ◽  
Vol 48 (4) ◽  
pp. 338-346
Author(s):  
Fernando Gomes BARBOSA ◽  
Marina Mariko SUGUI ◽  
Valéria Dornelles Gindri SINHORIN ◽  
Rogério de Campos BICUDO ◽  
Fernando Rafael de MOURA ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Micronucleus Test ◽  
Ethanolic Extract ◽  
Thiobarbituric Acid ◽  
Biological Study ◽  
Antimutagenic Effect ◽  
Test Protein ◽  
Polychromatic Erythrocytes ◽  
Markers Of Oxidative Stress

ABSTRACT Capirona decorticans (Rubiaceae) is popularly used to treat warts, wounds, mycoses and scabies, and is also a component of the Ayahuasca tea. Despite its popular use, the phytochemical and pharmacological research on this species is limited. Therefore, this work quantified phenolic compounds in the ethanolic extract (EE) and hydromethanolic fraction (FM) (406, 293 mgEAG g-1, respectively) from leaves of C. decorticans. We identified flavonoids by LC-MS/MS-MMR-ESI (apigenin, rutin, luteolin, miricetin, quercetin, quercetin-3-β-D-glucoside, quercetrin), and evaluated oxidative stress and mutagenic/antimutagenic effect of EE and FM through an in vivo experiment using Swiss mice and cyclophosphamide (CP) as an inducer of DNA damage and oxidative stress. Mice were pretreated for 15 consecutive days with EE or FM (250 mg kg-1) and then intraperitoneally injected with CP (25 mg kg-1). Carbonylated proteins, ascorbic acid, catalase and thiobarbituric acid-reactive substances were measured in hepatic and renal tissues. The mutagenic/antimutagenic effect was evaluated through the Micronucleus Test. Protein carbonylation in the liver of animals exposed to CP was reduced by FM. There was no significant effect on other markers of oxidative stress. The groups treated with the extracts showed a significant percentage reduction (EE = 96% and FM = 71%) in the frequency of micronucleated polychromatic erythrocytes induced by CP. EE showed mutagenicity when used alone. The EE and FM of C. decorticans leaves showed antioxidant potential equivalent to that observed in other species, did not cause oxidative stress, nor toxicity, and had a protective and antimutagenic effect, although the EE showed signs of mutagenicity.

scholarly journals AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathaniel B. Bone ◽  
Eugene J. Becker ◽  
Maroof Husain ◽  
Shaoning Jiang ◽  
Anna A. Zmijewska ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Inflammatory Responses ◽  
Abdominal Sepsis ◽  
Immune Defense ◽  
Bacterial Killing ◽  
Lung Infections ◽  
Sepsis Survivors ◽  
The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

scholarly journals Enhancing the Nrf2 Antioxidant Signaling Provides Protection Against Trichloroethene-mediated Inflammation and Autoimmune Response

2020 ◽  
Vol 175 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Nivedita Banerjee ◽  
Hui Wang ◽  
Gangduo Wang ◽  
M Firoze Khan
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Autoimmune Response ◽  
Mediated Effects ◽  
Antioxidant Gene Expression ◽  
Responsive Element

Abstract Trichloroethene (trichloroethylene, TCE) and one of its reactive metabolites dichloroacetyl chloride (DCAC) are associated with the induction of autoimmunity in MRL+/+ mice. Although oxidative stress plays a major role in TCE-/DCAC-mediated autoimmunity, the underlying molecular mechanisms still need to be delineated. Nuclear factor (erythroid-derived 2)-like2 (Nrf2) is an oxidative stress-responsive transcription factor that binds to antioxidant responsive element (ARE) and provides protection by regulating cytoprotective and antioxidant gene expression. However, the potential of Nrf2 in the regulation of TCE-/DCAC-mediated autoimmunity is not known. This study thus focused on establishing the role of Nrf2 and consequent inflammatory responses in TCE-/DCAC-mediated autoimmunity. To achieve this, we pretreated Kupffer cells (KCs) or T cells with/without tert-butylhydroquinone (tBHQ) followed by treatment with DCAC. In both KCs and T cells, DCAC treatment significantly downregulated Nrf2 and HO-1 expression along with induction of Keap-1 and caspase-3, NF-κB (p65), TNF-α, and iNOS, whereas pretreatment of these cells with tBHQ attenuated these responses. The in vitro findings were further verified in vivo by treating female MRL+/+ mice with TCE along with/without sulforaphane. TCE exposure in mice also led to reduction in Nrf2 and HO-1 but increased phospho-NF-κB (p-p65) and iNOS along with increased anti-dsDNA antibodies. Interestingly, sulforaphane treatment led to amelioration of TCE-mediated effects, resulting in Nrf2 activation and reduction in inflammatory and autoimmune responses. Our results show that TCE/DCAC mediates an impairment in Nrf2 regulation. Attenuation of TCE-mediated autoimmunity via activation of Nrf2 supports that antioxidants sulforaphane/tBHQ could be potential therapeutic agents for autoimmune diseases.

scholarly journals MyD88-Dependent Signaling Affects the Development of Meningococcal Sepsis by Nonlipooligosaccharide Ligands

2006 ◽  
Vol 74 (6) ◽  
pp. 3538-3546 ◽  
Author(s):  
Laura Plant ◽  
Hong Wan ◽  
Ann-Beth Jonsson
Keyword(s):  
Inflammatory Responses ◽  
Innate Immune ◽  
Meningococcal Sepsis ◽  
Wild Type ◽  
Microbial Infections ◽  
In The Wild ◽  
Myeloid Differentiation Factor ◽  
Dependent Pathway ◽  
Meningococcal Strain

ABSTRACT The Toll-like receptors (TLRs) and the adaptor myeloid differentiation factor 88 (MyD88) are important in the innate immune defenses of the host to microbial infections. Meningococcal ligands signaling via TLRs control inflammatory responses, and stimulation can result in fulminant meningococcal sepsis. In this study, we show that the responses to nonlipooligosaccharide (non-LOS) ligands of meningococci are MyD88 dependent. An isogenic LOS-deficient mutant of the serogroup C meningococcal strain FAM20 caused fatal disease in wild type C57BL/6 mice that was not observed in MyD88−/− mice. Fatality correlated with high proinflammatory cytokine and C5a levels in serum, high neutrophil numbers in blood, and increased bacteremia at 24 h postinfection in the wild-type mice. Infection with the parent strain FAM20 resulted in fatality in 100% of the wild-type mice and 50% of the MyD88−/− mice. We conclude that both LOS and another neisserial ligand cause meningococcal sepsis in an in vivo mouse model and confirm that meningococcal LOS can act via both the MyD88- dependent and -independent pathways, while the non-LOS meningococcal ligand(s) acts only via the MyD88-dependent pathway.

scholarly journals Loss of Sirt3 accelerates arterial thrombosis by increasing formation of neutrophil extracellular traps and plasma tissue factor activity

2018 ◽  
Vol 114 (8) ◽  
pp. 1178-1188 ◽  
Author(s):  
Daniel S Gaul ◽  
Julien Weber ◽  
Lambertus J van Tits ◽  
Susanna Sluka ◽  
Lisa Pasterk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Bone Marrow ◽  
Arterial Thrombosis ◽  
Ex Vivo ◽  
Neutrophil Extracellular Traps ◽  
Wild Type ◽  
Rotational Thromboelastometry ◽  
Extracellular Traps

AbstractAimsSirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI).Methods and resultsUsing a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3−/− mice (n = 6) was reduced by half compared to Sirt3+/+ wild-type (n = 8, P < 0.01) controls. Ex vivo analyses of whole blood using rotational thromboelastometry revealed accelerated clot formation and increased clot stability in Sirt3−/− compared to wild-type blood. rotational thromboelastometry of cell-depleted plasma showed accelerated clotting initiation in Sirt3−/− mice, whereas overall clot formation and firmness remained unaffected. Ex vivo LPS-induced neutrophil extracellular trap formation was increased in Sirt3−/− bone marrow-derived neutrophils. Plasma tissue factor (TF) levels and activity were elevated in Sirt3−/− mice, whereas plasma levels of other coagulation factors and TF expression in arterial walls remained unchanged. SOD2 expression in bone marrow -derived Sirt3−/− neutrophils was reduced. In STEMI patients, transcriptional levels of Sirt3 and its target SOD2 were lower in CD14+ leukocytes compared with healthy donors (n = 10 each, P < 0.01).ConclusionsSirt3 loss-of-function enhances experimental thrombosis in vivo via an increase of neutrophil extracellular traps and elevation of TF suggesting thrombo-protective effects of endogenous Sirt3. Acute coronary thrombosis in STEMI patients is associated with lower expression levels of SIRT3 and SOD2 in CD14+ leukocytes. Therefore, enhancing SIRT3 activity by pan-sirtuin activating NAD+-boosters may provide a novel therapeutic target to prevent or treat thrombotic arterial occlusion in myocardial infarction or stroke.

Abstract 123: Age-Related Endothelial Senescence is Driven by Thrombospondin-1-Activated NADPH Oxidase Nox1

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Daniel N Meijles ◽  
Imad Al Ghouleh ◽  
Sanghamitra Sahoo ◽  
Jefferson H Amaral ◽  
Heather Knupp ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Vascular Diseases ◽  
Dependent Manner ◽  
Wild Type ◽  
Molecular Control ◽  
Redox Biology ◽  
Age Related ◽  
P53 Activation

Organismal aging represents an independent risk factor underlying many vascular diseases, including systemic and pulmonary hypertension, and atherosclerosis. While the mechanisms driving aging are largely elusive, a steady persistent increase in tissue oxidative stress has been associated with senescence. Previously we showed TSP1 elicits NADPH oxidase (Nox)-dependent vascular smooth muscle cell oxidative stress. However mechanisms by which TSP1 affects endothelial redox biology are unknown. Here, we tested the hypothesis that TSP1 induces endothelial oxidative stress-linked senescence in aging. Using rapid autopsy disease-free human pulmonary (PA) artery, we identified a significant positive correlation between age, protein levels of TSP1, Nox1 and the cell-cycle repressor p21cip (p<0.05). Age also positively associated with increased Amplex Red-detected PA hydrogen peroxide levels (p<0.05). Moreover, treatment of human PA endothelial cells (HPAEC) with TSP1 (2.2nM; 24h) increased expression (~1.9 fold; p<0.05) and activation of Nox1 (~1.7 fold; p<0.05) compared to control, as assessed by Western blot and SOD-inhibitable cytochrome c reduction. Western blotting and immunofluorescence showed a TSP1-mediated increase in p53 activation, indicative of the DNA damage response. Moreover, TSP1 significantly increased HPAEC senescence in a p53/p21cip/Rb-dependent manner, as assessed by immunofluorescent detection of subcellular localization and senescence-associated β-galactosidase staining. To explore this pathway in vivo, middle-aged (8-10 month) wild-type and TSP1-null mice were utilized. In the TSP1-null, reduced lung senescence, oxidative stress, Nox1 levels and p21cip expression were observed compared to wild-type supporting findings in human samples and cell experiments. Finally, prophylactic treatment with specific Nox1 inhibitor NoxA1ds (10μM) attenuated TSP1-induced HPAEC ROS, p53 activation, p21cip expression and senescence. Taken together, our results provide molecular insight into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence, with implications for molecular control of the aging process.

scholarly journals Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1

2017 ◽  
Vol 114 (40) ◽  
pp. 10743-10748 ◽  
Author(s):  
Tali Mazor ◽  
Charles Chesnelong ◽  
Aleksandr Pankov ◽  
Llewellyn E. Jalbert ◽  
Chibo Hong ◽  
...  
Keyword(s):  
Copy Number ◽  
Cpg Island ◽  
Clonal Expansion ◽  
Low Grade ◽  
Copy Number Alterations ◽  
Wild Type ◽  
Mutant Idh1

IDH1 mutation is the earliest genetic alteration in low-grade gliomas (LGGs), but its role in tumor recurrence is unclear. Mutant IDH1 drives overproduction of the oncometabolite d-2-hydroxyglutarate (2HG) and a CpG island (CGI) hypermethylation phenotype (G-CIMP). To investigate the role of mutant IDH1 at recurrence, we performed a longitudinal analysis of 50 IDH1 mutant LGGs. We discovered six cases with copy number alterations (CNAs) at the IDH1 locus at recurrence. Deletion or amplification of IDH1 was followed by clonal expansion and recurrence at a higher grade. Successful cultures derived from IDH1 mutant, but not IDH1 wild type, gliomas systematically deleted IDH1 in vitro and in vivo, further suggestive of selection against the heterozygous mutant state as tumors progress. Tumors and cultures with IDH1 CNA had decreased 2HG, maintenance of G-CIMP, and DNA methylation reprogramming outside CGI. Thus, while IDH1 mutation initiates gliomagenesis, in some patients mutant IDH1 and 2HG are not required for later clonal expansions.

Lipid Peroxidation, Protein Oxidation, Gelatinases, and Their Inhibitors in a Group of Adults with Obesity

2019 ◽  
Vol 51 (06) ◽  
pp. 389-395 ◽  
Author(s):  
Gregorio Caimi ◽  
Baldassare Canino ◽  
Maria Montana ◽  
Caterina Urso ◽  
Vincenzo Calandrino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Protein Oxidation ◽  
Thiobarbituric Acid ◽  
Protein Carbonyl ◽  
The Body ◽  
Control Group ◽  
The Matrix ◽  
Markers Of Oxidative Stress ◽  
Obese Subjects

AbstractThe association between obesity and cardiovascular diseases has a multifactorial pathogenesis, including the synthesis of inflammatory molecules, the increase in oxidative stress and the dysregulation of the matrix metalloprotease (MMP) concentration and activity. In a group of adults with obesity, divided in 2 subgroups according to the body mass index (BMI), we examined lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), protein oxidation, expressed as protein carbonyl groups (PCs), plasma gelatinases (MMP-2 and MMP-9), and their tissue inhibitors (TIMP-1 and TIMP-2). In the whole group, as well as in the 2 subgroups (with BMI 30–35 or BMI>35) of obese subjects, we observed an increase in TBARS, PCs, MMP-2, and MMP-9, and also TIMP-1 and TIMP-2 in comparison with the control group. A positive correlation between TBARS and PCs emerged in obese subjects and persisted after dividing obese subjects according to BMI. The correlation between MMP-2 and TIMP-2 was not statistically significant, while a significant correlation was present between MMP-9 and TIMP-1. The correlations between the markers of oxidative stress (TBARS and PCs) and those of the MMP/TIMP profile indicated a more marked influence of protein oxidation on MMPs and TIMPs in comparison with TBARS. The innovative aspect of our study was the simultaneous evaluation of oxidative stress markers and MMP/TIMP profile in adult obese subjects. We observed significant alterations and correlations that may negatively influence the clinical course of the disease.

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