scholarly journals Influence of Endothelin 1 Receptor Blockers and a Nitric Oxide Synthase Inhibitor on Reactive Oxygen Species Formation in Rat Lungs

2016 ◽  
pp. 789-798 ◽  
Author(s):  
P. KLENIEWSKA ◽  
A. GORĄCA
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Receptor Blocker ◽  
Oxygen Species ◽  
Endothelin 1 ◽  
Tnf Α ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Prior Administration

This study was designated to estimate protective role of ETA and ETB receptor antagonist against endothelin 1 (ET-1)-induced oxidative stress in lungs and determine whether these effects are mediated by nitric oxide (NO) synthase. Experiments were performed on Wistar rats divided into the following groups: I – saline (0.9 % NaCl); II – ET-1 (3 μg/kg b.w.), III – BQ123 (1 mg/kg b.w.) + ET-1 (3 μg/kg b.w.), IV – BQ788 (3 mg/kg b.w.) + ET-1 (3 μg/kg b.w.), V – N-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg b.w.) + ET-1 (3 μg/kg b.w.). ETA and ETB receptor antagonists or L-NAME were administered 30 min before ET-1 injection. The levels of the following substances were measured in the lungs homogenates: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), reduced glutathione (GSH) and tumor necrosis factor-alpha (TNF-α). The results showed that ET-1 significantly increased TBARS, H2O2 (respectively: p<0.001, p<0.02) and TNF-α levels (p<0.02) and decreased the GSH level (p<0.01) vs. control group. On the other hand, prior administration of ETA receptor blocker (BQ123) significantly attenuated TBARS (p<0.01), H2O2 (p<0.02), TNF-α (p<0.02) and increased GSH (p<0.02) levels vs. ET-1. However, prior administration of ETB receptor blocker BQ788 did not cause significant changes in the: TBARS, H2O2 and TNF-α (p>0.05) levels, but significantly increased the GSH level and GSH/GSSG ratio (p<0.05). Administration of L-NAME significantly attenuated TBARS (p<0.001), H2O2 (p<0.05), TNF-α (p<0.01) and increased GSH (p<0.05) levels vs. ET-1. In conclusion, we demonstrated that ET-1 induced oxidative stress in the lungs is mediated by ETA receptors. ETA receptor blockage inhibited generation of free radicals and TNF-α and ameliorated antioxidant properties. Moreover, generation of reactive oxygen species is mediated by NOS in the lungs.

scholarly journals The role of oxidative/nitrosative stress in pathogenesis of paracetamol-induced toxic hepatitis

2010 ◽  
Vol 63 (11-12) ◽  
pp. 827-832 ◽  
Author(s):  
Tatjana Radosavljevic ◽  
Dusan Mladenovic ◽  
Danijela Vucevic ◽  
Rada Jesic-Vukicevic
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Kupffer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Severe Liver ◽  
Hepatocellular Necrosis

Introduction. Paracetamol is an effective analgesic/antipyretic drug when used at therapeutic doses. However, the overdose of paracetamol can cause severe liver injury and liver necrosis. The mechanism of paracetamol-induced liver injury is still not completely understood. Reactive metabolite formation, depletion of glutathione and alkylation of proteins are the triggers of inhibition of mitochondrial respiration, adenosine triphosphate depletion and mitochondrial oxidant stress leading to hepatocellular necrosis. Role of oxidative stress in paracetamol-induced liver injury. The importance of oxidative stress in paracetamol hepatotoxicity is controversial. Paracetamol induced liver injury cause the formation of reactive oxygen species. The potent sources of reactive oxygen are mitochondria, neutrophils, Kupffer cells and the enzyme xatnine oxidase. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in paracetamol-induced oxidative stress. The production of mitochondrial reactive oxygen species is increased, and the glutathione content is decreased in paracetamol overdose. Oxidative stress in mitochondria leads to mito?chondrial dysfunction with adenosine triphosphate depletion, increase mitochondrial permeability transition, deoxyribonu?cleic acid fragmentation which contribute to the development of hepatocellular necrosis in the liver after paracetamol overdose. Role of Kupffer cells in paracetamol-induced liver injury. Paracetamol activates Kupffer cells, which then release numerous cytokines and signalling molecules, including nitric oxide and superoxide. Kupffer cells are important in peroxynitrite formation. On the other hand, the activated Kupffer cells release anti-inflammatory cytokines. Role of neutrophils in paracetamol-induced liver injury. Paracetamol-induced liver injury leads to the accumulation of neutrophils, which release lysosomal enzymes and generate superoxide anion radicals through the enzyme nicotinamide adenine dinucleotide phosphate oxidase. Hydrogen peroxide, which is influenced by the neutrophil-derived enzyme myeloperoxidase, generates hypochlorus acid as a potent oxidant. Role of peroxynitrite in paracetamol-induced oxidative stress. Superoxide can react with nitric oxide to form peroxynitrite, as a potent oxidant. Nitrotyrosine is formed by the reaction of tyrosine with peroxynitrite in paracetamol hepatotoxicity. Conclusion. Overdose of paracetamol may produce severe liver injury with hepatocellular necrosis. The most important mechanisms of cell injury are metabolic activation of paracetamol, glutathione depletion, alkylation of proteins, especially mitochondrial proteins, and formation of reactive oxygen/nitrogen species.

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.

scholarly journals Reactive Oxygen Species (ROS) Metabolism and Nitric Oxide (NO) Content in Roots and Shoots of Rice (Oryza sativa L.) Plants under Arsenic-Induced Stress

Agronomy ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1014 ◽  
Author(s):  
Ernestina Solórzano ◽  
Francisco J. Corpas ◽  
Salvador González-Gordo ◽  
José M. Palma
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Oryza Sativa ◽  
Oryza Sativa L ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Antioxidative Systems ◽  
Ros Metabolism ◽  
As Stress

Arsenic (As) is a highly toxic metalloid for all forms of life including plants. Rice is the main food source for different countries worldwide, although it can take up high amounts of As in comparison with other crops, showing toxic profiles such as decreases in plant growth and yield. The induction of oxidative stress is the main process underlying arsenic toxicity in plants, including rice, due to an alteration of the reactive oxygen species (ROS) metabolism. The aim of this work was to gain better knowledge on how the ROS metabolism and its interaction with nitric oxide (NO) operate under As stress conditions in rice plants. Thus, physiological and ROS-related biochemical parameters in roots and shoots from rice (Oryza sativa L.) were studied under 50 μM arsenate (AsV) stress, and the involvement of the main antioxidative systems and NO in the response of plants to those conditions was investigated. A decrease of 51% in root length and 27% in plant biomass was observed with 50 μM AsV treatment, as compared to control plants. The results of the activity of superoxide dismutase (SOD) isozymes, catalase, peroxidase (POD: total and isoenzymatic), and the enzymes of the ascorbate–glutathione cycle, besides the ascorbate and glutathione contents, showed that As accumulation provoked an overall significant increase of most of them, but with different profiles depending on the plant organ, either root or shoot. Among the seven identified POD isozymes, the induction of the POD-3 in shoots under As stress could help to maintain the hydrogen peroxide (H2O2) redox homeostasis and compensate the loss of the ascorbate peroxidase (APX) activity in both roots and shoots. Lipid peroxidation was slightly increased in roots and shoots from As-treated plants. The H2O2 and NO contents were enhanced in roots and shoots against arsenic stress. In spite of the increase of most antioxidative systems, a mild oxidative stress situation appears to be consolidated overall, since the growth parameters and those from the oxidative damage could not be totally counteracted. In these conditions, the higher levels of H2O2 and NO suggest that signaling events are simultaneously occurring in the whole plant.

scholarly journals Kallistatin attenuates endothelial apoptosis through inhibition of oxidative stress and activation of Akt-eNOS signaling

2010 ◽  
Vol 299 (5) ◽  
pp. H1419-H1427 ◽  
Author(s):  
Bo Shen ◽  
Lin Gao ◽  
Yi-Te Hsu ◽  
Grant Bledsoe ◽  
Makato Hagiwara ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Oxygen Species ◽  
Phosphatidylinositol 3 Kinase ◽  
Reactive Oxygen Species Formation ◽  
Endothelial Apoptosis ◽  
Species Formation ◽  
Tnf Α

Kallistatin is a regulator of vascular homeostasis capable of controlling a wide spectrum of biological actions in the cardiovascular and renal systems. We previously reported that kallistatin inhibited intracellular reactive oxygen species formation in cultured cardiac and renal cells. The present study was aimed to investigate the role and mechanisms of kallistatin in protection against oxidative stress-induced vascular injury and endothelial cell apoptosis. We found that kallistatin gene delivery significantly attenuated aortic superoxide formation and glomerular capillary loss in hypertensive DOCA-salt rats. In cultured endothelial cells, kallistatin suppressed TNF-α-induced cellular apoptosis, and the effect was blocked by the pharmacological inhibition of phosphatidylinositol 3-kinase and nitric oxide synthase (NOS) and by the knockdown of endothelial NOS (eNOS) expression. The transduction of endothelial cells with adenovirus expressing dominant-negative Akt abolished the protective effect of kallistatin on endothelial apoptosis and caspase activity. In addition, kallistatin inhibited TNF-α-induced reactive oxygen species formation and NADPH oxidase activity, and these effects were attenuated by phosphatidylinositol 3-kinase and NOS inhibition. Kallistatin also prevented the induction of Bim protein and mRNA expression by oxidative stress. Moreover, the downregulation of forkhead box O 1 (FOXO1) and Bim expression suppressed TNF-α-mediated endothelial cell death. Furthermore, the antiapoptotic actions of kallistatin were accompanied by Akt-mediated FOXO1 and eNOS phosphorylation, as well as increased NOS activity. These findings indicate a novel role of kallistatin in the protection against vascular injury and oxidative stress-induced endothelial apoptosis via the activation of Akt-dependent eNOS signaling.

HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-α in cerebral vascular endothelial cells

2006 ◽  
Vol 291 (5) ◽  
pp. C897-C908 ◽  
Author(s):  
Shyamali Basuroy ◽  
Sujoy Bhattacharya ◽  
Dilyara Tcheranova ◽  
Yan Qu ◽  
Raymond F. Regan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Serum Deprivation ◽  
Oxygen Species ◽  
Tnf Α ◽  
Endogenous Protection ◽  
Cerebral Vascular

Tumor necrosis factor-α (TNF-α) causes oxidative stress and apoptosis in a variety of cell types. Heme oxygenase (HO) degrades heme to bilirubin, an antioxidant, and carbon monoxide (CO), a cell cycle modulator, and a vasodilator. Newborn pig cerebral microvascular endothelial cells (CMVEC) highly express constitutive HO-2. We investigated the role of HO-2 in protection against TNF-α-induced apoptosis in cerebral vascular endothelium. In CMVEC from mice and newborn pigs, 15 ng/ml TNF-α alone, or with 10 μg/ml cycloheximide (CHX) caused apoptosis detected by nuclear translocation of p65 NF-κB, caspase-3 activation, DNA fragmentation, cell-cell contact destabilization, and cell detachment. TNF-α did not induce HO-1 expression in CMVEC. CMVEC from HO-2 knockout mice showed greater sensitivity to apoptosis caused by serum deprivation and TNF-α than did wild-type mice. TNF-α increased reactive oxygen species generation, including hydrogen peroxide and superoxide radicals, as detected by dihydrorhodamine-123 and dihydroethidium. The TNF-α response was inhibited by superoxide dismutase and catalase suggesting apoptosis is oxidative stress related. Inhibition of endogenous HO-2 in newborn pig CMVEC increased oxidative stress and exaggerated apoptosis caused by serum deprivation and TNF-α. In HO-1-overexpressing CMVEC (HO-1 selective induction by cobalt portophyrin), TNF-α did not cause apoptosis. A CO-releasing compound, CORM-A1, and bilirubin blocked TNF-α-induced reactive oxygen species accumulation and apoptosis consistent with the antioxidant and antiapoptotic roles of the end products of HO activity. We conclude that HO-2 is critical for protection of cerebrovascular endothelium against apoptotic changes induced by oxidative stress and cytokine-mediated inflammation.

Oxidative Stress and Hypertension

2021 ◽  
Vol 128 (7) ◽  
pp. 993-1020
Author(s):  
Kathy K. Griendling ◽  
Livia L. Camargo ◽  
Francisco J. Rios ◽  
Rhéure Alves-Lopes ◽  
Augusto C. Montezano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Animal Models ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Antioxidant Systems ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Organ Systems

A link between oxidative stress and hypertension has been firmly established in multiple animal models of hypertension but remains elusive in humans. While initial studies focused on inactivation of nitric oxide by superoxide, our understanding of relevant reactive oxygen species (superoxide, hydrogen peroxide, and peroxynitrite) and how they modify complex signaling pathways to promote hypertension has expanded significantly. In this review, we summarize recent advances in delineating the primary and secondary sources of reactive oxygen species (nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial nitric oxide synthase, endoplasmic reticulum, and mitochondria), the posttranslational oxidative modifications they induce on protein targets important for redox signaling, their interplay with endogenous antioxidant systems, and the role of inflammasome activation and endoplasmic reticular stress in the development of hypertension. We highlight how oxidative stress in different organ systems contributes to hypertension, describe new animal models that have clarified the importance of specific proteins, and discuss clinical studies that shed light on how these processes and pathways are altered in human hypertension. Finally, we focus on the promise of redox proteomics and systems biology to help us fully understand the relationship between ROS and hypertension and their potential for designing and evaluating novel antihypertensive therapies.

scholarly journals The role of oxidative stress in alcoholic liver injury

2009 ◽  
Vol 62 (11-12) ◽  
pp. 547-553 ◽  
Author(s):  
Tatjana Radosavljevic ◽  
Dusan Mladenovic ◽  
Danijela Vucevic
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Kupffer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Alcoholic Liver Injury ◽  
Chronic Ethanol Consumption

Introduction. Oxidative stress plays an important role in pathogenesis of alcoholic liver injury. The main source of free oxygen species is cytochrome P450-dependent monooxygenase, which can be induced by ethanol. Role of cytochrome P4502E1 in ethanol-induced oxidative stress. Reactive oxygen species produced by this enzyme are more important in intracellular oxidative damage compared to species derived from activated phagocytes. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in alcohol-induced oxidative stress. Production of mitochondrial reactive oxygen species is increased, and glutathione content is decreased in chronically ethanolfed animals. Oxidative stress in mitochondria leads to mitochondrial DNA damage and has a dual effect on apoptosis. Role of Kupffer cells in alcohol-induced liver injury. Chronic ethanol consumption is associated with increased release of endotoxin from gut lumen into portal circulation. Endotoxin activates Kupffer cells, which then release proinflammatory cytokines and oxidants. Role of neutrophils in alcohol-induced liver injury. Alcoholic liver injury leads to the accumulation of neutrophils, which release reactive oxygen species and lysosomal enzymes and contribute to hepatocyte damage and necrosis. Role of nitric oxide in alcohol-induced oxidative stress. High amounts of nitric oxide contribute to the oxidative damage, mainly by generating peroxynitrites. Role of antioxidants in ethanol-induced oxidative stress. Chronic ethanol consumption is associated with reduced liver glutathione and ?-tocopherol level and with reduced superoxide dismutase, catalase and glutathione peroxidase activity. Conclusion. Oxidative stress in alcoholic liver disease is a consequence of increased production of oxidants and decreased antioxidant defense in the liver.

scholarly journals Autocrine effects of endothelin-1 on leukocyte-endothelial interaction: stimulation of endothelin B receptor subtype reduces endothelial adhesiveness via a nitric oxide-dependent mechanism

Blood ◽  
1996 ◽  
Vol 88 (10) ◽  
pp. 3894-3900 ◽  
Author(s):  
T Murohara ◽  
AM Lefer
Keyword(s):  
Nitric Oxide ◽  
Receptor Antagonist ◽  
Receptor Subtype ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Endothelin B ◽  
Eta Receptor Antagonist ◽  
Inhibition Of Thrombin

The effects of endothelin-1 (ET-1) on P-selectin-mediated leukocyte endothelial interaction were examined in vitro. Adherence of autologous polymorphonuclear leukocytes (PMNs) to the endothelium was markedly enhanced by endothelial stimulation with either (2 U/mL) thrombin, (1 mumol/L) histamine, or (100 nmol/L) phorbol myristate acetate (PMA). In contrast, ET-1 alone (10 and 100 nmol/L) only slightly increased the number of adhering PMNs. The increased PMN adherence to thrombin- or histamine-stimulated endothelium, which was blocked by an anti-P-selectin monoclonal antibody, was also significantly attenuated by preincubation of coronary segments with (100 nmol/L) ET-1. We further investigated the mechanism of this anti-adherence action of ET-1 on thrombin-stimulated endothelial adhesiveness. Preincubation of coronary segments with a selective ETA receptor antagonist, BQ485 (1 mumol/L), had no effect on ET-1 inhibition of thrombin-induced PMN adherence. In contrast, preincubation with a selective ETB receptor antagonist, BQ788 (1 mumol/L) significantly reversed ET-1 inhibition of thrombin-induced PMN adherence, whereas the selective ETB receptor agonist BQ-3020 mimicked the inhibitory action of ET-1 on thrombin-induced PMN adherence. Furthermore, (100 mumol/L) N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, significantly attenuated ET-1 inhibition of thrombin-stimulated PMN adherence. These results suggest that ET-1 may inhibit P-selectin-mediated leukocyte-endothelial interaction via ETB receptor stimulation and subsequent endothelial NO formation. This autocrine effect of ET-1 may be involved in pathophysiologic states such as early atherogenesis by preventing leukocyte-endothelial interaction in constricted blood vessels.

Interaction among ET-1, endothelium-derived nitric oxide, and prostacyclin in pulmonary arteries and veins

1994 ◽  
Vol 267 (1) ◽  
pp. H139-H147 ◽  
Author(s):  
T. M. Zellers ◽  
J. McCormick ◽  
Y. Wu
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Potent Vasoconstrictor ◽  
Eta Receptor Antagonist ◽  
Arteries And Veins

Endothelin-1 causes vasodilation of the intact porcine pulmonary vascular bed. To determine the cause of this vasodilation, we investigated the interactions of endothelin-1 (ET-1), endothelium-derived nitric oxide (EDNO), and prostacyclin in isolated small porcine pulmonary arteries and veins under in vitro conditions. ET-1 caused concentration-dependent contractions in arteries and veins, augmented by the nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine, in pulmonary veins. BQ-123 (ETA-receptor antagonist) depressed the ET-1-induced contractions. Sarafotoxin S6C, an ETB-receptor agonist, caused contractions of pulmonary veins only. Endothelium-dependent relaxations to bradykinin and ET-1 were greater in pulmonary veins compared with arteries, inhibited by N omega-nitro-L-arginine, and reversed by L-arginine. BQ-123 augmented ET-1-induced arterial relaxation. ET-3 and sarafotoxin S6C, ETB-receptor agonists, caused comparable endothelium-dependent relaxations in arteries and veins. ET-1 caused a fourfold greater increase in prostacyclin release in pulmonary veins compared with arteries. We conclude that ET-1 is a potent vasoconstrictor of porcine pulmonary vessels and stimulates the release of EDNO and prostacyclin, which oppose the contractions to the peptide. The release of these endothelium-derived vasodilators appears greater in pulmonary veins.

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