scholarly journals Reactive oxygen species modulate growth of cerebral aneurysms: a study using the free radical scavenger edaravone and p47phox−/− mice

2009 ◽  
Vol 89 (7) ◽  
pp. 730-741 ◽  
Author(s):  
Tomohiro Aoki ◽  
Masaki Nishimura ◽  
Hiroharu Kataoka ◽  
Ryota Ishibashi ◽  
Kazuhiko Nozaki ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Free Radical ◽  
Cerebral Aneurysms ◽  
Reactive Oxygen ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Oxygen Species

Endotoxin Potentiates Cocaine-Mediated Hepatotoxicity by Nitric Oxide and Reactive Oxygen Species

2003 ◽  
Vol 22 (4) ◽  
pp. 305-316 ◽  
Author(s):  
Ramez Labib ◽  
Rita Turkall ◽  
Mohamed S. Abdel-Rahman
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Free Radical ◽  
Kupffer Cells ◽  
Oxidant Stress ◽  
Treatment Protocol ◽  
Reactive Oxygen ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Hydroxyl Free Radical

Exposure to small, noninjurious doses of the inflammagen, bacterial endotoxin (lipopolysaccharide, LPS) augments the toxicity of certain hepatotoxicants, including cocaine. The mechanism of this interaction has not been clearly elucidated, but it seems that aspects of the inflammatory response initiated by exposure to LPS may be responsible. In particular, this study examined the role of Kupffer cells and the modulating effects of nitric oxide (NO) and reactive oxygen species (ROS) on the LPS potentiation of cocaine-mediated hepatotoxicity (CMH). Mice were administered oral cocaine hy-drochloride for 5 consecutive days at a dose of 20 mg/kg with and without 12 times 106 EU LPS/kg given intraperitoneally (IP) 4 hours after the last cocaine injection. Pretreatment regimens consisted of administration of 300 mg/kg, IP, of aminoguanidine (AM) or 1,3-dimethylthiourea (DMU) at 1 hour or 15 minutes, respectively, before each cocaine administration. In another group, mice were pretreated with saline using the same cocaine and LPS treatment protocol, but received a single pretreatment of 7 mg gadolinium chloride (Gd Cl3)/kg intravenously (IV), or sterile saline 24 hours prior to the LPS administration. The Gd Cl3 (Kupffer cell inhibitor) pretreatment inhibited the LPS potentiation of CMH, but did not reverse the effects of cocaine alone. On the other hand, AM (NO synthase inhibitor), decreased the synthesis of NO as observed by the decrease in the plasma nitrate/nitrite level and completely reversed the hepatotoxic effects of cocaine and LPS alone and in combination. Moreover, DMU (hydroxyl free radical scavenger) ameliorated the effects of cocaine and significantly reduced the hepatotoxicity observed with the cocaine and LPS administration. These data suggest that cocaine sensitizes the liver and subsequent activation of Kupffer cells by LPS leads to the formation of increased levels of NO, which can promote oxidant stress and thus provide an environment favoring the generation of more reactive species such as the hydroxyl free radical.

Effects of reactive oxygen species on prostacyclin production in perinatal rat lung cells

1989 ◽  
Vol 66 (3) ◽  
pp. 1321-1327 ◽  
Author(s):  
D. S. Lee ◽  
E. A. McCallum ◽  
D. M. Olson
Keyword(s):  
Reactive Oxygen Species ◽  
Glucose Oxidase ◽  
Reactive Oxygen ◽  
Radical Scavenger ◽  
Lung Cells ◽  
Oxygen Species ◽  
Rat Lung ◽  
Lactate Dehydrogenase Release ◽  
Culture Model

A differentiation-arrested primary cell culture model was used to examine the role of reactive oxygen species in the control of prostacyclin (PGI2) production in the perinatal rat lung. Coincubation of the lung cells with arachidonic acid (AA) and xanthine (X, 0.25 mM) plus xanthine oxidase (XO, 10 mU/ml) or with AA and glucose (25 mM) plus glucose oxidase (25 mU/ml) augmented the AA-induced PGI2 output. Superoxide dismutase (10 U/ml) did not alter the X + XO effect, whereas catalase (10 U/ml) eliminated both X + XO and glucose plus glucose oxidase effects. H2O2 (1–200 microM) showed a dose-related biphasic augmentation with peak stimulation at 20 microM. Catalase again blocked this effect, but dimethylthiourea, a hydroxyl radical scavenger, did not. A 20-min pretreatment of the cells with X + XO, glucose plus glucose oxidase, or H2O2, however, diminished the capacity of the cells to convert exogenous AA to PGI2. This pretreatment effect was also blocked by catalase. The responses were similar in lung cells obtained from day 20 rat fetuses (term = 22 days) and 1-day-old newborn rats. Lactate dehydrogenase release was not detected during treatment periods but increased significantly after exposure to reactive oxygen species.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of Noxa Via Generation of Reactive Oxygen Species Plays a Key Role in Induction of CLL Cell Apoptosis by Two Novel p53-Independent Cytotoxic Agents.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2752-2752
Author(s):  
Andrew Steele ◽  
Archibald G Prentice ◽  
Anastasios Chanalaris ◽  
A. Victor Hoffbrand ◽  
Kate Cwynarski ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Apoptosis ◽  
Conflicts Of Interest ◽  
Reactive Oxygen ◽  
Cytotoxic Agents ◽  
Ros Generation ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Independent Manner ◽  
Factor C

Abstract Abstract 2752 Poster Board II-728 Approximately 15% of CLL patients present with a deletion of chromosome 17p, resulting in the loss of the p53 gene. The percentage of 17p-deleted patients can increase to between 30–50% following treatment with cytotoxic agents which induce CLL apoptosis via upregulation of p53. Therefore, identification of novel agents which kill CLL cells independently of p53 is of crucial importance. We have recently shown that two chemically unrelated agents, 2-phenylacetylenesulfonamide (PAS) and the sesquiterpene lactone LC1 kill CLL cells regardless of the functional status of p53. Furthermore, in contrast to the conventional drugs chlorambucil and fludarabine, PAS and LC1 induce apoptosis in the absence of p53 elevation. However, the mechanisms of action by which these agents induce p53-independent apoptosis are unclear. We have previously shown that both PAS and LC1 initiated CLL cell apoptosis within 6-10h with, maximal killing by 48h. Here we show that treatment of CLL cells with either agent results in the generation of reactive oxygen species (ROS), the activating phosphorylation of the pro-apoptotic MAP kinase family member JNK (Fig 1), resulting in turn in upregulation of its downstream target, the transcription factor c-JUN (Fig 2). The BH3-only pro-apoptotic protein Noxa was originally described as a pro-apoptotic target for upregulation by p53. However, both PAS (Figs1 and 2) and LC1 upregulated Noxa in a p53-independent manner. Addition of N-acetylcysteine (NAC), a free radical scavenger, decreased ROS generation by PAS or LC1 and also prevented phosphorylation of JNK and Noxa upregulation (Fig 1) and also the upregulation of c-JUN. NAC also strikingly abrogated apoptosis induction by either agent, as shown by quantitation of cleavage of the caspase 3 substrate poly (ADP ribose) polymerase (PARP; Fig 1). Taken together, the data suggest both PAS and LC1 induce p53-independent apoptosis via upregulation of ROS and the subsequent induction of Noxa. The data are also compatible with a role for JNK and c-JUN in the events leading to Noxa upregulation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Reactive Oxygen Species and Induction of Lignin Peroxidase in Phanerochaete chrysosporium

2003 ◽  
Vol 69 (11) ◽  
pp. 6500-6506 ◽  
Author(s):  
Paula A. Belinky ◽  
Nufar Flikshtein ◽  
Sergey Lechenko ◽  
Shimon Gepstein ◽  
Carlos G. Dosoretz
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Damage ◽  
Phanerochaete Chrysosporium ◽  
Hydroxyl Radicals ◽  
Lignin Peroxidase ◽  
Manganese Superoxide Dismutase ◽  
Reactive Oxygen ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Atmospheric Air

ABSTRACT We studied oxidative stress in lignin peroxidase (LIP)-producing cultures (cultures flushed with pure O2) of Phanerochaete chrysosporium by comparing levels of reactive oxygen species (ROS), cumulative oxidative damage, and antioxidant enzymes with those found in non-LIP-producing cultures (cultures grown with free exchange of atmospheric air [control cultures]). A significant increase in the intracellular peroxide concentration and the degree of oxidative damage to macromolecules, e.g., DNA, lipids, and proteins, was observed when the fungus was exposed to pure O2 gas. The specific activities of manganese superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase and the consumption of glutathione were all higher in cultures exposed to pure O2 (oxygenated cultures) than in cultures grown with atmospheric air. Significantly higher gene expression of the LIP-H2 isozyme occurred in the oxygenated cultures. A hydroxyl radical scavenger, dimethyl sulfoxide (50 mM), added to the culture every 12 h, completely abolished LIP expression at the mRNA and protein levels. This effect was confirmed by in situ generation of hydroxyl radicals via the Fenton reaction, which significantly enhanced LIP expression. The level of intracellular cyclic AMP (cAMP) was correlated with the starvation conditions regardless of the oxygenation regimen applied, and similar cAMP levels were obtained at high O2 concentrations and in cultures grown with atmospheric air. These results suggest that even though cAMP is a prerequisite for LIP expression, high levels of ROS, preferentially hydroxyl radicals, are required to trigger LIP synthesis. Thus, the induction of LIP expression by O2 is at least partially mediated by the intracellular ROS.

scholarly journals Reactive oxygen species and antioxidant defense in puromycin aminonucleoside glomerulopathy.

1997 ◽  
Vol 8 (11) ◽  
pp. 1722-1731 ◽  
Author(s):  
W Gwinner ◽  
U Landmesser ◽  
R P Brandes ◽  
B Kubat ◽  
J Plasger ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Antioxidant Enzymes ◽  
Hydroxyl Radical ◽  
Antioxidant Defense ◽  
Reactive Oxygen ◽  
Initial Increase ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Puromycin Aminonucleoside

Results from several radical scavenger studies indirectly suggested an involvement of reactive oxygen species in the pathogenesis of puromycin aminonucleoside glomerulopathy. In this study, generation of reactive oxygen species was examined directly in glomeruli isolated from rats in the acute phase of puromycin aminonucleoside nephrosis and related to the changes in the glomerular antioxidant defense. Five and nine days after puromycin aminonucleoside injection, gross proteinuria, reduced creatinine clearances, and typical changes of glomerular morphology were present. Levels of reactive oxygen species were increased eightfold in glomeruli isolated 15 min after puromycin aminonucleoside injection, returned to baseline levels on days 1 and 5 after injection, and rose again to 14-fold on day 9 after injection, as determined by chemiluminescence with luminol. Further analysis of increased glomerular radical generation, using the chemiluminescence enhancer lucigenin and different radical scavengers, suggested a predominant involvement of hydroxyl radical and hydrogen peroxide in the initial increase in reactive oxygen species 15 min after puromycin aminonucleoside. Nine days after induction of nephrosis, primarily superoxide anion and hydroxyl radical were found to contribute to increased reactive oxygen species. Despite oxidative stress, antioxidant enzymes were not induced in the course of nephrosis. On the contrary, catalase and glutathione peroxidase activities declined 9 d after puromycin aminonucleoside injection. The results indicate that a transient increase in glomerular reactive oxygen species is sufficient to induce the oxidative glomerular injury observed in this model and that the glomerulus may not necessarily respond to oxidative stress with an induction of antioxidant enzymes.

CD36 Mediated Reactive Oxygen Species Formation Contributes to Thrombosis.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1901-1901
Author(s):  
Wei Li ◽  
Maria Febbraio ◽  
Roy L. Silverstein
Keyword(s):  
Reactive Oxygen Species ◽  
Carotid Artery ◽  
Vessel Wall ◽  
Carotid Arteries ◽  
Reactive Oxygen ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Carotid Artery Injury ◽  
Artery Injury ◽  
Ros Formation

Abstract We previously showed that mice in which the CD36 gene was deleted had significantly prolonged time to form an occlusive thrombus in response to FeCl3-induced vascular injury than wild type (WT) mice. In other studies we and others have shown that CD36 promotes reactive oxygen species (ROS) formation in murine models of cerebral and cardiac ischemia. In this study, we examined the formation and roles of ROS in FeCl3-induced carotid artery injury and thrombosis using CD36 null and WT mice. Hydroethidine, a fluorescent superoxide indicator, was injected via the jugular vein and then carotid artery injury was induced in the contralateral artery by direct topical application of FeCl3 at concentrations of 7.5% or 12.5%. Fluorescence images were monitored with intravital microscopy. FeCl3 dose dependently induced significant accumulation of ROS in the vessel wall; however, the degree was significantly less in CD36 null mice than in WT mice exposed to the lower dose of FeCl3. Direct injection of Edavarone (1 mg/Kg body weight), a free radical scavenger, significantly elongated the time to thrombosis in WT mice. Thrombosis time was also increased in the CD36 null mice, but not to the same extent as WT. We also found fewer endothelial cell-derived microparticles (CD105 positive) in plasma of CD36 null mice 3 minutes after injury with the low dose of FeCl3. Immunoblots of lysates prepared from carotid arteries with thrombi or from untreated normal carotid arteries showed that levels of peroxiredoxin 2 (Prx 2), an antioxidant enzyme known to detoxify ROS, were lower in the thrombi formed from CD36 null mice, but higher in the normal vessel wall, suggesting that an anti-oxidative system may exist in the vessel wall of CD36 null mice. We conclude that CD36 plays a role in ROS formation during thrombosis and may also sensitize the vessel to injury induced by FeCl3. High Prx 2 expression in the vessel wall in CD36 null mice may contribute to the anti-oxidative effect observed in these mice.

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