scholarly journals Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jaroslaw Dudka ◽  
Franciszek Burdan ◽  
Agnieszka Korga ◽  
Magdalena Iwan ◽  
Barbara Madej-Czerwonka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome P450 ◽  
Xanthine Oxidase ◽  
Lipid Peroxidation Product ◽  
Glutathione Level ◽  
Oxidative Damages ◽  
Peroxidation Product ◽  
Oxide Synthase ◽  
Doxorubicin Administration ◽  
Inducible Nitric Oxide

Cytochrome P450 NADPH-reductase (P450R), inducible synthase (iNOS) and xanthine oxidase play an important role in the antracycline-related cardiotoxicity. The expression of P450R and iNOS is regulated by triiodothyronine. The aim of this study was to evaluate the effect of methimazole-induced hypothyreosis on oxidative stress secondary to doxorubicin administration. 48 hours after methimazole giving cessation, rats were exposed to doxorubicin (2.0, 5.0 and 15 mg/kg). Blood and heart were collected 4, 48 and 96 h after the drug administration. Animals exposed exclusively to doxorubicin or untreated ones were also assessed. The hypothyreosis (0.025% of methimazole) significantly increased the doxorubicin effect on the cardiac carbonyl group and they may increase the glutathione level. An insignificant effect of methimazole was noticed in case of the cardiac lipid peroxidation product, the amount of DNA oxidative damages, iNOS and xanthine oxidase-enzymes responsible for red-ox activation of doxorubicin. However, the concentration of P450R was affected by a lower dose of methimazole in rats administered with doxorubicin. Since in rats receiving doxorubicin changes in oxidative stress caused by methimazole were not accompanied by elevation of bioreductive enzymes, it may be concluded that these changes in the oxidative stress were not related to the tested enzymes.

Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury

2021 ◽  
pp. 096032712199944
Author(s):  
Mohamed IA Hassan ◽  
Fares EM Ali ◽  
Abdel-Gawad S Shalkami
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Liver Enzymes ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Aim: Hepatic ischemia/reperfusion (I/R) injury is a syndrome involved in allograft dysfunction. This work aimed to elucidate carvedilol (CAR) role in hepatic I/R injury. Methods: Male rats were allocated to Sham group, CAR group, I/R group and CAR plus I/R group. Rats subjected to hepatic ischemia for 30 minutes then reperfused for 60 minutes. Oxidative stress markers, inflammatory cytokines and nitric oxide synthases were measured in hepatic tissues. Results: Hepatocyte injury following I/R was confirmed by a marked increase in liver enzymes. Also, hepatic I/R increased the contents of malondialdehyde however decreased glutathione contents and activities of antioxidant enzymes. Furthermore, hepatic I/R caused elevation of toll-like receptor-4 (TLR-4) expression and inflammatory mediators levels such as tumor necrosis factor-α, interleukin-6 and cyclooxygenase-II. Hepatic I/R caused down-regulation of endothelial nitric oxide synthase and upregulation of inducible nitric oxide synthase expressions. CAR treatment before hepatic I/R resulted in the restoration of liver enzymes. Administration of CAR caused a significant correction of oxidative stress and inflammation markers as well as modulates the expression of endothelial and inducible nitric oxide synthase. Conclusions: CAR protects liver from I/R injury through reduction of the oxidative stress and inflammation, and modulates endothelial and inducible nitric oxide synthase expressions.

Abstract 316: Effects of Inhibiting of Inducible Nitric Oxide Synthase in the Pathophysiology of Experimental Preeclampsia

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Lorena M Amaral ◽  
Ana Carolina T Palei ◽  
Lucas C Pinheiro ◽  
Jonas T Sertorio ◽  
Danielle A Guimaraes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
Oxygen Species ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The pathophysiology of preeclampsia (PE) is not entirely known. However, increased oxidative stress possibly leading to impaired nitric oxide activity has been implicated in the critical condition. Increased oxidative stress with increased levels of highly reactive species including superoxide may generate peroxynitrite. We examined the role of inducible nitric oxide synthase (iNOS) and oxidative stress in the reduced uterine perfusion pressure (RUPP) preeclampsia experimental model. METHODS: RUPP was induced in wistar rats. Pregnant rats in the RUPP group had their aortic artery clipped at day 14 of gestation. After a midline incision, a silver clip (0.203 mm) was placed around the aorta above the iliac bifurcation; silver clips (0.100 mm) were also placed on branches of both the right and left ovarian arteries that supply the uterus. Sham-operated (pregnant control rats) and RUPP rats were treated with oral vehicle or 1 mg/kg/day 1400W (iNOS inhibitor) for 5 days. Mean arterial pressure (MAP) and plasma levels of thiobarbituric acid-reactive species (TBARS) and total radical-trapping antioxidant potential (TRAP) were measured determined. Aortic iNOS expression (Western blotting) and reactive oxygen species (ROS; assessed by fluorescence microscopy with dihydroethidium-DHE) were measured. We found increased mean arterial pressure in RUPP compared with pregnant control rats (MAP= 128±1 vs. 100±1.8 mmHg, respectively; P<0.05) and 1400W exerted antihypertensive effects (MAP= 114±2 vs.128±1 mmHg in RUPP treated and untreated rats, respectively; P<0.05). Higher reactive oxygen species (ROS) concentrations were found in RUPP compared with pregnant control rats (7.1±0.5 vs. 5.1±0.5 arbitrary units (A.U.), respectively; P<0.05) and 1400W decreased ROS production to 5.8±0.02 A.U. in RUPP treated rats, P<0.05. In addition, 1400W attenuated iNOS expression in RUPP rats (0.29±0.02 vs. 0.55±0.8 A.U. in RUPP treated and untreated rats, respectively; P<0.01) and had no effects on plasma TBARS and TRAP levels. Our results suggest that 1400w exerts antihypertensive effects in the RUPP model and suppresses ROS formation. Supported by FAPESP,Cnpq.

Abstract 5702: Oxidative Stress in Patients with Lone Atrial Fibrillation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kengo Kusano ◽  
Kazufumi Nakamura ◽  
Tohru Ohe
Keyword(s):  
Oxidative Stress ◽  
Atrial Fibrillation ◽  
Immunohistochemical Analysis ◽  
Lipid Peroxidation Product ◽  
Lone Atrial Fibrillation ◽  
Activated T Cells ◽  
Mhc I ◽  
Mhc Ii ◽  
Peroxidation Product ◽  
Ros Formation

Background: Lone atrial fibrillation (LAF) is a common arrhythmia, but its mechanism and the aggravated factor of arrhythmia are poorly understood. Oxidative stress has been implicated in the pathogenesis of heart failure. We have previously demonstrated that the amount of 4-hydroxy-2-nonenal (HNE) modified protein, which is a major lipid peroxidation product and a cytotoxic aldehyde, causes intracellular Ca2+ overload via reactive oxygen species (ROS) formation in cardiomyocytes and leads to develop arrhythmia. Accordingly we examined the levels of HNE and major histocompatibility complex (MHC) with the disease severity in LAF patients. Method: Atrial and ventricular myocardial samples were obtained from twelve patients (11 men and 1 woman, mean 48±14 years old) by endomyocardial biopsy in 10, autopsy sample in 1 and surgical resection sample in 1. Histological assessments and immunohistochemical analysis for HNE modified protein, MHC class-I and -II antigens (grade 0 to 3) were performed and compared with LAF severity. Results: Histological assessment showed that increased number of interstitial cells (mainly activated T cells) was observed only in the atrium but not in the ventricle. Moderate to severe expression of MHC antigens (grade 2 or 3) was more observed in the atrium than the ventricle (MHC-I: seven in atrium and three in ventricle; MHC-II: ten in atrium and four in ventricle). Atrial myocarditis was detected in 6 out of 11 samples. HNE modified protein was also more observed in the atrium than that in the ventricle. In addition, more severe expression of HNE staining was observed in the samples from persistent/chronic LAF than that in paroxysmal LAF. Conclusion: These data indicates that oxidative stress plays an important role as an aggravating factor in LAF patients.

scholarly journals Aminoguanidine Protects Boar Spermatozoa against the Deleterious Effects of Oxidative Stress

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 212 ◽  
Author(s):  
Eliana Pintus ◽  
Martin Kadlec ◽  
Marija Jovičić ◽  
Markéta Sedmíková ◽  
José Ros-Santaella
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Agent ◽  
Antioxidant Properties ◽  
In Vitro Effects ◽  
Oxide Synthase ◽  
Boar Spermatozoa ◽  
Generating System ◽  
Control Samples ◽  
Inducible Nitric Oxide

Aminoguanidine is a selective inhibitor of the inducible nitric oxide synthase (iNOS) and a scavenger of reactive oxygen species (ROS). Numerous studies have shown the antioxidant properties of aminoguanidine in several cell lines, but the in vitro effects of this compound on spermatozoa under oxidative stress are unknown. In this study, we tested the hypothesis that aminoguanidine may protect against the detrimental effects of oxidative stress in boar spermatozoa. For this purpose, sperm samples were incubated with a ROS generating system (Fe2+/ascorbate) with or without aminoguanidine supplementation (10, 1, and 0.1 mM). Our results show that aminoguanidine has powerful antioxidant capacity and protects boar spermatozoa against the deleterious effects of oxidative stress. After 2 h and 3.5 h of sperm incubation, the samples treated with aminoguanidine showed a significant increase in sperm velocity, plasma membrane and acrosome integrity together with a reduced lipid peroxidation in comparison with control samples (p < 0.001). Interestingly, except for the levels of malondialdehyde, the samples treated with 1 mM aminoguanidine did not differ or showed better performance than control samples without Fe2+/ascorbate. The results from this study provide new insights into the application of aminoguanidine as an in vitro therapeutic agent against the detrimental effects of oxidative stress in semen samples.

scholarly journals Carotid intima-media thickness and oxidative stress markers for assessment of atherosclerosis in children with β thalassemia major

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Geetanjali Jindal ◽  
Prashant Chavan ◽  
Ravinder Kaur ◽  
Shivani Jaswal ◽  
Kamal Kumar Singhal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Oxidized Ldl ◽  
Thalassemia Major ◽  
Lipid Peroxidation Product ◽  
Oxidative Stress Markers ◽  
Lipoprotein A ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Peroxidation Product

<p>The present study evaluates carotid intimamedia thickness (CIMT) in children with β thalassemia major to assess atherosclerosis and its relation to the underlying proposed causative mechanisms <em>via</em> lipid peroxidation product malondialdehyde (MDA), oxidized lowdensity lipoproteins (LDL), total antioxidant level, and lipid profile. A cross sectional study was conducted on 62 children (31 cases and 31 controls). CIMT by high resolution ultrasound and biochemical parameters <em>i.e.</em>, total cholesterol, triglycerides, high-density lipoproteins, LDL, Oxidized LDL, lipoprotein (a), lipid peroxidation product MDA and total antioxidant were measured in enrolled subjects and compared. In our study, CIMT was significantly increased in β thalassemia major patients’ as compared to healthy controls. Mean CIMT in cases was 0.69±0.11 mm and in controls 0.51±0.07 mm. Mean oxidized LDL (EU/mL) in cases 39.3±34.4 (range 14.4 to 160) was significantly raised (P=0.02, t test) as compared to controls 23.9±13.4 (range 12 to 70). In our study we found MDA levels (nmol/mL) to be increased in β thalassemia patients as compared to controls. Mean MDA was 10.0±3.27 (4.41 to 17.48) in cases while in controls was 6.87±4.55 (1.5 to 17.9). Our study results show CIMT as an early marker of atherogenesis in β thalassemia major. Oxidative stress markers are also increased in β thalassemia major patients and lipoprotein (a) shows a positive correlation with CIMT. The present study points towards various atherogenetic mechanisms in β thalassemia major.</p><p> </p><p>本研究评价β重型地中海贫血患儿颈动脉内膜中层厚度（CIMT），以评估动脉粥样硬化，以及与潜在通过血脂过氧化反应产物丙二醛（MDA）、氧化低密度脂蛋白（LDL）、总抗氧化水平和血脂谱所提出致病机制之间的关系。 在62名儿童（31例病例和31例对照）中进行了一项横断面研究。 在入组受试者中通过高分辨率超声和生化指标（即总胆固醇、甘油三酯、高密度脂蛋白、LDL、氧化LDL，脂蛋白（a）、血脂过氧化产物MDA和总抗氧化剂）测量CIMT并进行比较。 在我们的研究中，CIMT在β重型地中海贫血患者中比健康对照组显著增加。 病例组中的平均CIMT为0.69±0.11 mm，对照组0.51±0.07 mm。病例组中平均氧化LDL（EU/mL）为39.3±34.4（从14.4到160的范围）与对照组的23.9±13.4（12至70的范围）相比显著升高（P = 0.02，t检验）。 在我们的研究中，我们发现β地中海贫血患者中的MDA水平（nmol/mL）比对照组更高。 病例组中的平均MDA为10.0±3.27（4.41至17.48），而对照组为6.87±4.55（1.5到17.9）。 我们的研究结果表明，CIMT是β重型地中海贫血动脉粥样硬化的早期标记物。 氧化应激标记物在β重型地中海贫血患者中也有增加，脂蛋白（a）显示出与CIMT呈正相关。 本研究针对β重型地中海贫血中的各种动脉粥样硬化机制。</p>

scholarly journals Vitamin D Deficiency Aggravates Hepatic Oxidative Stress and Inflammation during Chronic Alcohol-Induced Liver Injury in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Chun-Qiu Hu ◽  
Qing-Li Bo ◽  
Lan-Lan Chu ◽  
Yong-Di Hu ◽  
Lin Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Liver Injury ◽  
Vitamin D Deficiency ◽  
Chronic Alcohol ◽  
Cytokines And Chemokines ◽  
Hepatic Oxidative Stress ◽  
Oxide Synthase ◽  
Etoh Group ◽  
Inducible Nitric Oxide

Vitamin D deficiency has been reported in alcoholics. This study is aimed at evaluating the effects of vitamin D deficiency on chronic alcohol-induced liver injury in mice. Mice were fed with modified Lieber-DeCarli liquid diets for 6 weeks to establish an animal model of chronic alcohol-induced liver injury. In the VDD+EtOH group, mice were fed with modified diets, in which vitamin D was depleted. Vitamin D deficiency aggravated alcohol-induced liver injury. Furthermore, vitamin D deficiency aggravated hepatocyte apoptosis during alcohol-induced liver injury. Although it has a little effect on hepatic TG content, vitamin D deficiency promoted alcohol-induced hepatic GSH depletion and lipid peroxidation. Further analysis showed that vitamin D deficiency further increased alcohol-induced upregulation of hepatic inducible nitric oxide synthase (inos), two NADPH oxidase subunits p47phox and gp91phox, and heme oxygenase- (HO-) 1. By contrast, vitamin D deficiency attenuated alcohol-induced upregulation of hepatic antioxidant enzyme genes, such as superoxide dismutase (sod) 1 and gshpx. In addition, vitamin D deficiency significantly elevated alcohol-induced upregulation of hepatic proinflammatory cytokines and chemokines. Taken together, these results suggest that vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-induced liver injury.

scholarly journals Network Pharmacology-Based Antioxidant Effect Study of Zhi-Zi-Da-Huang Decoction for Alcoholic Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Li An ◽  
Fang Feng
Keyword(s):  
Liver Disease ◽  
Xanthine Oxidase ◽  
Alcoholic Liver Disease ◽  
Effect Study ◽  
Network Pharmacology ◽  
Target Network ◽  
Bioactive Ingredients ◽  
Stress Damage ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Zhi-Zi-Da-Huang decoction (ZZDHD), a classic traditional Chinese medicine (TCM) formula, has been used for centuries to treat alcoholic liver disease. Reliable therapeutics of ZZDHD has also been validated in clinical practice. In this study, molecular docking and network analysis were carried out to explore the antioxidative mechanism of ZZDHD as an effective therapeutic approach to treat alcoholic liver disease. Multiple active compounds of ZZDHD were screened based on four key original enzymes (cytochrome P450 2E1, xanthine oxidase, inducible nitric oxide synthase, and cyclooxygenase-2) involved in ethanol-induced oxidative stress damage. A drug-target network was constructed through network pharmacology analysis, which predicted the relationships of active ingredients to the targets. Some results had been verified by the previous experimental pharmacological studies; meanwhile, it was first reported that xanthine oxidase and eriocitrin, neoeriocitrin, isorhoifolin, and poncirin had interactions. The network pharmacology strategy used provided a forceful tool for searching the mechanism of action of TCM formula and novel bioactive ingredients.

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