Abstract 107: Apocynin Attenuates Isoproterenol-induced Myocardial Injury: Implications For Targeting Nadph Oxidase In Myocardial Fibrogenesis

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Yu Chen ◽  
Jingang Cui ◽  
Qinbo Yang ◽  
Chenglin Jia ◽  
Minqi Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Myocardial Fibrosis ◽  
Myocardial Injury ◽  
Oxidase Inhibitor ◽  
Ros Generation ◽  
Dependent Manner ◽  
Expression Of Genes ◽  
Therapeutic Development ◽  
Myocardial Injuries

Myocardial fibrosis results from cardiac injuries caused by various pathophysiological mechanisms including myocardial infarction, leading to destruction of myocardial architecture and progressive cardiac dysfunction. Oxidative stress is likely involved in myocardial ischemic injury and the subsequent tissue remodeling mediated by myocardial fibrogenesis. Our current study aimed to evaluate the implication of NADPH oxidase in overproduction of reactive oxygen species and its contribution to the pathogenesis of myocardial fibrogenesis after ischemic injuries. The effects of Apocynin, a selective NADPH oxidase inhibitor, were evaluated in the mouse model of isoproterenol-induced myocardial injury by histopathological approaches and whole-genome gene expression profiling. The results demonstrated that Apocynin was able to inhibit the development of ISO-induced myocardial necrotic lesions and fibrogenesis in a dose-dependent manner. Moreover, the preventive effects of Apocynin on myocardial injuries were associated with suppressed expression of genes implicated in inflammation responses and extracellular matrix, which were remarkably upregulated by isoproterenol administration. In summary, o ur study provides proof-of-concept for the involvement of NADPH oxidase-mediated ROS generation in myocardial ischemic injuries and fibrogenesis, which will benefit the mechanism-based therapeutic development targeting NADPH oxidase and oxidative stress in treating myocardial fibrosis and related disorders.

PKC-δ-dependent activation of oxidative stress in adipocytes of obese and insulin-resistant mice: role for NADPH oxidase

2005 ◽  
Vol 288 (2) ◽  
pp. E405-E411 ◽  
Author(s):  
Ilana Talior ◽  
Tamar Tennenbaum ◽  
Toshio Kuroki ◽  
Hagit Eldar-Finkelman
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Oxidase Inhibitor ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Ros Generation ◽  
Ros Production ◽  
Insulin Resistant ◽  
Glucose Depletion ◽  
Causative Factors

Oxidative stress is thought to be one of the causative factors contributing to insulin resistance and type 2 diabetes. Previously, we showed that reactive oxygen species (ROS) production is significantly increased in adipocytes from high-fat diet-induced obese and insulin-resistant mice (HF). ROS production was also associated with the increased activity of PKC-δ. In the present studies, we hypothesized that PKC-δ contributes to ROS generation and determined their intracellular source. NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) reduced ROS levels by 50% in HF adipocytes, and inhibitors of NO synthase (l-NAME, 1 mM), xanthine oxidase (allopurinol, 100 μM), AGE formation (aminoguanidine, 10 μM), or the mitochondrial uncoupler (FCCP, 10 μM) had no effect. Rottlerin, a selective PKC-δ inhibitor, suppressed ROS levels by ∼50%. However, neither GÖ-6976 nor LY-333531, effective inhibitors toward conventional PKC or PKC-β, respectively, significantly altered ROS levels in HF adipocytes. Subsequently, adenoviral-mediated expression of wild-type PKC-δ or its dominant negative mutant (DN-PKC-δ) in HF adipocytes resulted in either a twofold increase in ROS levels or their suppression by 20%, respectively. In addition, both ROS levels and PKC-δ activity were sharply reduced by glucose depletion. Taken together, these results suggest that PKC-δ is responsible for elevated intracellular ROS production in HF adipocytes, and this is mediated by high glucose and NADPH oxidase.

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes

1998 ◽  
Vol 274 (1) ◽  
pp. C245-C252 ◽  
Author(s):  
Junsuke Igarashi ◽  
Masashi Nishida ◽  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Hiroaki Kosaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiac Myocytes ◽  
Myocardial Injury ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor ◽  
Oxide Synthase ◽  
Gpx Activity

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

scholarly journals NADPH Oxidase Inhibitor Apocynin Attenuates PCB153-Induced Thyroid Injury in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ablikim Abliz ◽  
Chen Chen ◽  
Wenhong Deng ◽  
Weixing Wang ◽  
Rongze Sun
Keyword(s):  
Thyroid Hormone ◽  
Nadph Oxidase ◽  
Inflammatory Cytokines ◽  
Thyroid Dysfunction ◽  
Thyroid Tissue ◽  
Oxidase Inhibitor ◽  
Control Group ◽  
Ros Generation ◽  
Sprague Dawley ◽  
Serum Thyroid Hormone

PCBs, widespread endocrine disruptors, cause the disturbance of thyroid hormone (TH) homeostasis in humans and animals. However, the exact mechanism of thyroid dysfunction caused by PCBs is still unknown. In order to clarify the hypotheses that NADPH oxidase (NOX) and subsequent NF-κB pathway may play roles in thyroid dysfunction, sixty Sprague-Dawley rats were randomly divided into four groups: control group, PCB153 treated (PCB) group, received apocynin with PCB153 treatment (APO + PCB) group, and drug control (APO) group. Serum thyroid hormone levels were evaluated. The morphological change of thyroid tissue was analyzed under the light and transmission electron microscopy. NOX2, 8-OHdG, and NF-κB expression in the thyroid tissue was evaluated by immune-histochemical staining. Oxidative stress and inflammatory cytokines were detected. The following results were reduced after apocynin treatment: (1) serum thyroid hormone, (2) thyroid pathological injuries, (3) thyroid MDA, (4) thyroid ultrastructural change, (5) serum inflammatory cytokines, and (6) thyroid expression of NOX2, 8-OHdG, and NF-κB. These results suggested that NOX inhibition attenuates thyroid dysfunction induced by PCB in rats, presumably because of its role in preventing ROS generation and inhibiting the activation of NF-κB pathway. Our findings may provide new therapeutic targets for PCBs induced thyroid dysfunction.

The NADPH oxidase inhibitor apocynin induces nitric oxide synthesis via oxidative stress

2008 ◽  
Vol 228 (3) ◽  
pp. 277-285 ◽  
Author(s):  
Chiara Riganti ◽  
Costanzo Costamagna ◽  
Sophie Doublier ◽  
Erica Miraglia ◽  
Manuela Polimeni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Oxidase Inhibitor ◽  
Nitric Oxide Synthesis ◽  
Nadph Oxidase Inhibitor

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 ANTIOXIDANT AND HEPATOPROTECTIVE EFFECT OF SWERTIA CHIRATA ON HYPOXIA-INDUCED OXIDATIVE STRESS IN WISTAR RATS

2019 ◽  
Vol 12 (1) ◽  
pp. 76
Author(s):  
Kritika Kaushal ◽  
Harvinder Singh ◽  
Anil Kant Thakur
Keyword(s):  
Oxidative Stress ◽  
Liver Function ◽  
Wistar Rats ◽  
Hepatic Damage ◽  
Ros Generation ◽  
Dependent Manner ◽  
Traditional Use ◽  
Hydroalcoholic Extract ◽  
Swertia Chirata ◽  
Liver Functions

Objective: Swertia chirata has been used in traditional and folklore medicine to treat several ailments such as hepatic disorders. However, the mechanistic and experimental justification to its traditional use is lacking. The present study was aimed to investigate the hepatoprotective potential of S. chirata during hypoxia (HYP)-induced hepatic damage in Wistar rats and to determine the underlying mechanism.Methods: Hydroalcoholic extract of S. chirata was prepared using Soxhlet extraction. Animals were divided into six groups (n=5). Animals in the HYP groups were subjected to HYP for 3 days (10% O2) to induce oxidative stress and hepatic damage. 50 and 100 mg/kg extract treatments were provided orally once daily for 7 days after which animals were sacrificed, and biochemical investigations for oxidative stress, liver function tests, and hepatic histopathology were performed.Results: HYP-induced marked oxidative stress as indicated by the significantly elevated mitochondrial ROS generation, lipid peroxidation, glutathione, and depleted catalase levels. Liver function test indicated hepatic damage as the levels of serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, and aspartate transaminase were significantly elevated in HYP animals. S. chirata treatment alleviated oxidative stress and improved liver functions in a dose-dependent manner. Liver histopathology confirmed the marked hepatic damage induced by HYP and revealed that S. chirata efficiently rescued liver from hypoxic damage.Conclusion: Hydroalcoholic extract of S. chirata is a potent hepatoprotective intervention which was associated with its potential to alleviate oxidative stress and improve liver functions. Moreover, it could find clinical application as a safer and alternative remedy for liver ailments.

scholarly journals Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia

2016 ◽  
Vol 213 (9) ◽  
pp. 1851-1864 ◽  
Author(s):  
Keer Sun ◽  
Vijaya Kumar Yajjala ◽  
Christopher Bauer ◽  
Geoffrey A. Talmon ◽  
Karl J. Fischer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Influenza Infection ◽  
Treatment Strategies ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Inflammatory Cells ◽  
Oxidase Inhibitor ◽  
Lung Damage ◽  
Surrounding Tissue ◽  
Staphylococcus Aureus Pneumonia

Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)–deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress–associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress increased necrotic death of inflammatory cells, thereby resulting in lethal damage to surrounding tissue. Collectively, our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation. This disruption leads to not only increased susceptibility to S. aureus infection, but also extensive lung damage. Importantly, we show that combination treatment of antibiotic and NADPH oxidase inhibitor significantly improved animal survival from coinfection. These findings suggest that treatment strategies that target both bacteria and oxidative stress will significantly benefit patients with influenza-complicated S. aureus pneumonia.

scholarly journals 17β-Estradiol Modulates SIRT1 and Halts Oxidative Stress-Mediated Cognitive Impairment in a Male Aging Mouse Model

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 928 ◽  
Author(s):  
Mehtab Khan ◽  
Rahat Ullah ◽  
Shafiq Ur Rehman ◽  
Shahid Ali Shah ◽  
Kamran Saeed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Memory Impairment ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ros Generation ◽  
Dependent Manner ◽  
Molecular Docking Study ◽  
17Β Estradiol

Oxidative stress has been considered the main mediator in neurodegenerative disease and in normal aging processes. Several studies have reported that the accumulation of reactive oxygen species (ROS), elevated oxidative stress, and neuroinflammation result in cellular malfunction. These conditions lead to neuronal cell death in aging-related neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease. Chronic administration of d-galactose (d-gal) for a period of 10 weeks causes ROS generation and neuroinflammation, ultimately leading to cognitive impairment. In this study, we evaluated the estrogen receptor α (ERα)/silent mating type information regulation 2 homolog 1 (SIRT1)-dependent antioxidant efficacy of 17β-estradiol against d-gal-induced oxidative damage-mediated cognitive dysfunction in a male mouse model. The results indicate that 17β-estradiol, by stimulating ERα/SIRT1, halts d-gal-induced oxidative stress–mediated JNK/NF-ҡB overexpression, neuroinflammation and neuronal apoptosis. Moreover, 17β-estradiol ameliorated d-gal-induced AD-like pathophysiology, synaptic dysfunction and memory impairment in adult mouse brains. Interestingly, inhibition of SIRT1 with Ex527 (a potent and selective SIRT1 inhibitor) further enhanced d-gal-induced toxicity and abolished the beneficial effect of 17β-estradiol. Most importantly, for the first time, our molecular docking study reveals that 17β-estradiol allosterically increases the expression of SIRT1 and abolishes the inhibitory potential of d-ga. In summary, we can conclude that 17β-estradiol, in an ERα/SIRT1-dependent manner, abrogates d-gal-induced oxidative stress–mediated memory impairment, neuroinflammation, and neurodegeneration in adult mice.

scholarly journals Protective effects of delphinidin against H2O2–induced oxidative injuries in human retinal pigment epithelial cells

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Timin Ni ◽  
Wanju Yang ◽  
Yiqiao Xing
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Ros Generation ◽  
Dependent Manner ◽  
Pigment Epithelial ◽  
Age Related

Abstract Age-related macular degeneration (AMD) is now one of the leading causes of blindness in the elderly population and oxidative stress-induced damage to retinal pigment epithelial (RPE) cells occurs as part of the pathogenesis of AMD. In the present study, we evaluated the protective effect of delphinidin (2-(3,4,5-trihydroxyphenyl) chromenylium-3,5,7-triol) against hydrogen peroxide (H2O2)-induced toxicity in human ARPE-19 cells and its molecular mechanism. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry demonstrated that pretreatment of ARPE-19 cells with delphinidin (25, 50, and 100 μg/ml) significantly increased cell viability and reduced the apoptosis from H2O2 (0.5 mM)-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cytochrome c, and caspase-3 protein expression and enhancement of Bcl-2 protein. The same tendency was observed in ARPE-19 cells pre-treated with 15 mM of N-acetylcysteine (NAC) before the addition of H2O2. Furthermore, pre-incubation of ARPE-19 cells with delphinidin markedly inhibited the intracellular reactive oxygen species (ROS) generation and Nox1 protein expression induced by H2O2. Moreover, the decreased antioxidant enzymes activities of superoxide dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GSH-PX) and elevated (MDA) level in H2O2-treated cells were reversed to the normal standard by the addition of delphinidin, which was regulated by increasing nuclear Nrf2 protein expression in ARPE-19 cells. Our results suggest that delphinidin effectively protects human ARPE-19 cells from H2O2-induced oxidative damage via anti-apoptotic and antioxidant effects.

scholarly journals ANG II promotes autophagy in podocytes

2010 ◽  
Vol 299 (2) ◽  
pp. C488-C496 ◽  
Author(s):  
Anju Yadav ◽  
Sridevi Vallabu ◽  
Shitij Arora ◽  
Pranay Tandon ◽  
Divya Slahan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Ang Ii ◽  
Electron Microscopic ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Microscopic Studies ◽  
Autophagic Process

Podocytes are an integral and important constituent of the glomerular filtration barrier (GFB) and are exposed to a higher concentrations of ANG II in diseased states; consequently, podocytes may accumulate oxidized proteins and damaged mitochondria. In the present study, we evaluated the effect of ANG II on the podocyte autophagic process, which is likely to be triggered in order to degrade unwanted proteins and damaged organelles. To quantitate the occurrence of autophagy, electron microscopic studies were carried out on control and ANG II-treated conditionally immortalized mouse podocytes (CIMPs). ANG II-treated cells showed a fivefold greater number of autophagosomes/field compared with control cells. This proautophagic effect of ANG II was inhibited by pretreatment with 3-methyladenine, an inhibitor of autophagy. ANG II also enhanced podocyte expression of autophagic genes such as LC3-2 and beclin-1. Since oxidative stress is often associated with the induction of autophagy, we examined the effect of ANG II on podocyte reactive oxygen species (ROS) generation. ANG II enhanced podocyte ROS generation in a time-dependent manner. To determine whether there is a causal relationship between ANG II-induced oxidative stress and induction of autophagy, we evaluated the effect of antioxidants on ANG II-induced autophagy. As expected, the proautophagic effect of ANG II was inhibited by antioxidants. We conclude that ANG II promotes podocyte autophagy through the generation of ROS.

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