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1.

001-es BibID:BIBFORM014284
Első szerző:Bai Péter (biokémikus)
Cím:Matrix metalloproteinase activation is an early event in doxorubicin-induced cardiotoxicity / Péter Bai, Jon G. Mabley, Lucas Liaudet, László Virág, Csaba Szabó, Pál Pacher
Dátum:2004
ISSN:0891-5849 (Print)
Megjegyzések:Matrix metalloproteinase (MMP) activation contributes to the development of various pathophysiological conditions, including dilated cardiomyopathy, congestive heart failure, and reperfusion injury. Increased oxidative and nitrosative stress have been implicated in the activation of MMPs and also in the cardiotoxicity of doxorubicin (DOX), a commonly used antitumor agent. Thus, we hypothesized that MMP activation occurs in DOX-induced cardiotoxicity. Male Balb/c mice received a single injection of DOX (25 mg/kg i.p.) and were sacrificed 12 h, 1, 2, 3 and 4 days later. Hearts and aortae were harvested for MMP zymography. DOX induced time-dependent activation of MMPs both in the heart and in the aortic tissue with an earlier onset in the latter. These results demonstrate that MMP activation is an early event in DOX-induced cardiotoxicity and raises the possibility that MMP inhibitors may influence the outcome of this severe complication.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
Antineoplastic Agents/toxicity
Biological Markers/analysis
Cardiomyopathy, Dilated/chemically induced/enzymology
Doxorubicin/ toxicity
Enzyme Activation
Heart/ drug effects
Heart Failure/chemically induced
Male
Matrix Metalloproteinases/ metabolism0891-5849
Mice
Mice, Inbred BALB C
Models, Animal
Myocardium/enzymology/ pathology
Reperfusion Injury/chemically induced/enzymology
Acute Disease
Catalysis/drug effects
Chronic Disease
Creatine Kinase/blood
Disease Models, Animal
Enzyme Inhibitors/pharmacology
Heart/ drug effects/physiopathology
Heart Failure/ chemically induced/physiopathology/prevention & control
L-Lactate Dehydrogenase/blood
Metalloporphyrins/ pharmacology
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide Synthase/antagonists & inhibitors/genetics/metabolism
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Oxidative Stress/drug effects/genetics
Peroxynitrous Acid/ metabolism
Survival Rate
Antibiotics, Antineoplastic
Creatine Kinase/metabolism
Doxorubicin
Enzyme Activation/drug effects
Heart Failure/ chemically induced/pathology/physiopathology
Hemodynamics/drug effects
L-Lactate Dehydrogenase/metabolism
Metalloendopeptidases/metabolism
Poly(ADP-ribose) Polymerases/ genetics/ metabolism
Survival Analysis
Ventricular Function, Left/genetics
Apoptosis
Benzamides/ pharmacology
Caspases/metabolism
Cells, Cultured
DNA Damage/drug effects
DNA Fragmentation/drug effects
Enzyme Activation/drug effects/physiology
Enzyme Inhibitors/ pharmacology
Mitochondria/ drug effects
Nitrates
Nitrites/toxicity
Nitrogen Oxides/ toxicity
Poly(ADP-ribose) Polymerases/ antagonists & inhibitors/metabolism
Protective Agents/ pharmacology
Thymus Gland/cytology/ drug effects
Tyrosine
Megjelenés:Oncology reports. - 11 : 2 (2004), p. 505-508. -
További szerzők:Mabley, Jon G. Liaudet, Lucas Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Szabó Csaba Pacher Pál
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2.

001-es BibID:BIBFORM028397
Első szerző:Eaves-Pyles, Tonyia
Cím:Flagellin, a novel mediator of Salmonella-induced epithelial activation and systemic inflammation : I kappa B alpha degradation, induction of nitric oxide synthase, induction of proinflammatory mediators, and cardiovascular dysfunction / Tonyia Eaves-Pyles, Kanneganti Murthy, Lucas Liaudet, László Virág, Gary Ross, Francisco Garcia Soriano, Csaba Szabó, Andrew L. Salzman
Dátum:2001
ISSN:1550-6606
Megjegyzések:Gram-negative sepsis is mediated by the actions of proinflammatory genes induced in response to microbes and their products. We report that flagellin, the monomeric subunit of flagella, is a potent proinflammatory species released by Salmonella. Flagellin (1 microgram/ml) induces IkappaBalpha degradation, NF-kappaB nuclear translocation, and inducible NO synthase expression in cultured intestinal epithelial cells (IEC). Aflagellic Salmonella mutants do not induce NF-kappaB activation or NO production by cultured IEC. Antiserum to flagellin blocks NO production in IEC induced by medium conditioned by a variety of motile Gram-negative enteric pathogens (Escherichia coli, Salmonella muenchen, Serratia marcescens, Proteus mirabilis, and Proteus vulgaris). Flagellin, when injected systemically (approximately 10 microgram/mouse), induces systemic inflammation characterized by the systemic expression of a range of proinflammatory cytokines and chemokines and of inducible NO synthase. At higher doses (approximately 300 microgram/mouse), flagellin induces shock, characterized by hypotension, reduced vascular contractility in mice, and death. The effects of flagellin do not diminish in C3H/HeJ LPS-resistant mice, indicating that the Toll-like receptor-4 receptor is not involved in flagellin's actions. In LPS-resistant mice, i.p. injection of S. dublin flagellin or medium conditioned by wild-type S. dublin induces serum IFN-gamma and TNF-alpha, whereas medium conditioned by aflagellic mutants has no effect. Flagellin can be detected in the blood of rats with septic shock induced by live bacteria at approximately 1 microg/ml. We propose that flagellin released by Gram-negative pathogens may contribute to the inflammatory response by an LPS- and Toll-like receptor-4-independent pathway.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Immunology 166 : 2 (2001), p. 1248-1260. -
További szerzők:Murthy, Kanneganti G. Liaudet, Lucas Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Ross, Gary Soriano, Francisco Garcia Szabó Csaba (1967-) (orvos) Salzman, Andrew L.
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3.

001-es BibID:BIBFORM014259
Első szerző:Jagtap, Prakash
Cím:Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents / Jagtap, P., Soriano, F. G., Virag, L., Liaudet, L., Mabley, J., Szabo, E., Hasko, G., Marton, A., Lorigados, C. B., Gallyas, F., Jr., Sumegi, B., Hoyt, D. G., Baloglu, E., VanDuzer, J., Salzman, A. L., Southan, G. J., Szabo, C.
Dátum:2002
ISSN:0090-3493 (Print)
Megjegyzések:To synthesize novel inhibitors of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) synthetase (PARS), also known as poly(ADP-ribose) polymerase (PARP), and to test them in in vitro models of oxidant-induced cytotoxicity and in endotoxin and splanchnic occlusion-reperfusion-induced shock. DESIGN: Randomized, prospective laboratory study. SETTING: Research laboratory. SUBJECTS: Murine macrophages, thymocytes, and endothelial cells; Balb/c mice and Wistar rats. INTERVENTIONS: Macrophages and endothelial cells were treated with peroxynitrite and bleomycin to induce PARS activation, and thymocytes were treated with peroxynitrite to induce cell necrosis. Novel PARS inhibitors were synthesized and used to reduce PARS activation and to reverse cytotoxicity. Balb/c mice were subjected to splanchnic occlusion and reperfusion and were pretreated with various doses (1-10 mg/kg intraperitoneally) of PJ34, a selected, potent, water-soluble PARS inhibitor. The passage of fluorescein isothiocyanate-conjugated dextran (4 kDa) was analyzed in everted gut ileal sacs incubated ex vivo as an index of gut permeability. Wistar rats were subjected to Escherichia coli bacterial lipopolysaccharide (40 mg/kg intraperitoneally). PJ34 was also used at 10 mg/kg intraperitoneally, 1 hr before lipopolysaccharide or at 25 mg/kg intraperitoneally 1 hr after lipopolysaccharide treatment. Serum concentrations of indicators or multiple organ injury, concentrations of various proinflammatory mediators, and tissue concentrations of myeloperoxidase and malondialdehyde were measured. In addition, survival rates and vascular contractile and relaxant responses were recorded. MEASUREMENTS AND MAIN RESULTS: Appropriate modifications of the phenanthridinone core structure yielded significant increases in the potency of the compounds, both as PARS inhibitors and as cytoprotective agents. The compound N-(6-oxo-5,6-dihydro-phenanthridin-2-yl) -N,N-dimethylacetamide (designated as PJ34) was one of the potent PARS inhibitors of the series, and it dose-dependently protected against thymocyte necrosis, with a half-maximal restoration of cell viability of 35 nM and complete protection at 200 nM. PARS activation also was visualized by immunohistochemistry and was dose-dependently suppressed by PJ34. The effect of PJ34 was dose-dependently reversed by excess nicotinamide adenine dinucleotide (oxidized). The PARS inhibitors dose-dependently suppressed proinflammatory cytokine and chemokine production and restored viability in immunostimulated macrophages. PJ34 was selected for the subsequent in vivo studies. PJ34 significantly protected against splanchnic reperfusion-induced intestinal hyperpermeability in the mouse. PJ34 reduced peak plasma concentrations of tumor necrosis factor-alpha, interleukin-1beta, and nitrite/nitrate in the plasma of lipopolysaccharide-treated rats. PJ34 ameliorated the lipopolysaccharide-induced increases in indexes of liver and kidney failure and concentrations of myeloperoxidase and malondialdehyde in the lung and gut. Lipopolysaccharide elicited vascular dysfunction, which was normalized by PJ34. Lipopolysaccharide-induced mortality was reduced by PJ34 (both pre- and posttreatment). CONCLUSIONS: The novel series of phenanthridinone PARS inhibitors have potent cytoprotective effects in vitro and significant protective effects in shock and reperfusion injury in rodent models in vivo.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
Bleomycin/pharmacology
Cells, Cultured
*Cytoprotection
Dose-Response Relationship, Drug
Enzyme Activation
Enzyme Inhibitors/*pharmacology
külföldön készült közlemény
Interleukin-1/blood
Kidney/chemistry
Lipopolysaccharides/pharmacology
Lung/chemistry
Malondialdehyde/analysis
Mice
Mice, Inbred BALB C
Nitrates/blood
Nitrites/blood
Peroxidase/analysis
Peroxynitrous Acid/pharmacology
Phenanthrenes/*pharmacology
Poly(ADP-ribose) Polymerases/*antagonists & inhibitors
Rats
Rats, Wistar
Shock/*prevention & control
Tumor Necrosis Factor-alpha/analysis
Megjelenés:Critical Care Medicine. - 30 : 5 (2002), p. 1071-1082. -
További szerzők:Soriano, Francisco Garcia Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Liaudet, Lucas Mabley, Jon G. Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Haskó György (1967-) (biokémikus) Marton, A. Lorigados, Clara Batista Gallyas Ferenc Jr Sümegi Balázs Hoyt, Dale G. Baloglu, Erkan VanDuzer, John Salzman, Andrew L. Southan, Garry J. Szabó Csaba
Internet cím:elektronikus változat
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4.

001-es BibID:BIBFORM040005
Első szerző:Liaudet, Lucas
Cím:Suppression of poly (ADP-ribose) polymerase activation by 3-aminobenzamide in a rat model of myocardial infarction : long term morphological and functional consequences / Liaudet, L., Szabó, É., Timashpolsky, L., Virág, L., Cziráki, A., Szabó, C.
Dátum:2001
ISSN:0007-1188
Megjegyzések:1. Recent studies demonstrated that inhibition or genetic inactivation of the enzyme poly (ADP-ribose) polymerase (PARP) is beneficial in myocardial reperfusion injury. PARP activation in the reperfused myocardium has been assumed, but not directly demonstrated. Furthermore, the issue whether pharmacological PARP inhibition affords long-term functional benefit in the reperfused myocardium has not been explored. These questions were addressed in the present study. 2. In a rat model of myocardial ischemia (1 h) and reperfusion (up to 24 h), there was a marked and significant activation of PARP in the ischemic borderzone, as determined by poly(ADP-ribose) (PAR) immunohistochemistry. PAR localized to the nuclei of myocytes and infiltrating mononuclear cells. In the core of the infarction, necrotic tissues and diffuse PAR staining were observed. PARP activation remained markedly detectable 24 h after reperfusion. The PARP inhibitor 3-aminobenzamide (20 mg kg(-1) intraperitoneally 10 min before reperfusion, and every 2 h thereafter for 6 h) markedly reduced the activation of the enzyme in myocytes. 3. 3-aminobenzamide significantly protected against myocardial morphological and functional alterations at 24 h post-reperfusion. Notably, infarct size was reduced, circulating creatine kinase activity was attenuated, and myocardial contractility (dP dt(-1)) was restored by 3-aminobenzamide. 4. Our results demonstrate a significant and prolonged activation of PARP in the reperfused myocardium, localizing to the necrotic area and the ischaemic borderzone. Furthermore, the studies demonstrate that PARP inhibition affords long-term beneficial morphological and functional effects in the reperfused myocardium. These data strengthen the notion that pharmacological PARP inhibition is a viable novel experimental approach for protection against myocardial reperfusion injury.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:British Journal Of Pharmacology. - 133 : 8 (2001), p. 1424-1430. -
További szerzők:Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Timashpolsky, Leonid Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Cziráki Attila Szabó Csaba
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DOI
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5.

001-es BibID:BIBFORM028548
Első szerző:Liaudet, Lucas
Cím:Inosine exerts a broad range of antiinflammatory effects in a murine model of acute lung injury / Lucas Liaudet, Jon G. Mabley, Pál Pacher, László Virág, Francisco G. Soriano, Anita Marton, György Haskó, Edwin A. Deitch, Csaba Szabó
Dátum:2002
ISSN:0003-4932
Megjegyzések:OBJECTIVE: To investigate the effects of inosine on the acute lung inflammation induced by lipopolysaccharide (LPS) in vivo and on the activation and cytotoxicity elicited by proinflammatory cytokines on human lung epithelial (A549) cells in vitro. SUMMARY BACKGROUND DATA: Inosine is an endogenous purine recently shown to exert immunomodulatory and antiinflammatory effects. METHODS: Mice challenged with intratracheal LPS (50 microg) were treated after 1, 6, and 12 hours with inosine (200 mg/kg intraperitoneal) or vehicle. After 24 hours, bronchoalveolar lavage fluid was obtained to measure proinflammatory (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1beta, IL-6), and antiinflammatory (IL-10, IL-4) cytokines, chemokines (MIP-1alpha and MIP-2), myeloperoxidase activity and total cell counts, nitric oxide production, and proteins. Lung histology and immunohistochemical detection of 3-nitrotyrosine, a marker of nitrosative stress, were performed in inflated-fixed lungs. In vitro, cell viability and production of the chemokine IL-8 were evaluated in A549 cells stimulated with a mixture of cytokines in the presence or absence of inosine. RESULTS: Inosine downregulated the LPS-induced expression of TNF-alpha, IL-1beta, IL-6 and MIP-2 and tended to reduce MIP-1alpha, whereas it enhanced the production of IL-4. Total leukocyte counts, myeloperoxidase, nitric oxide production, and proteins were all significantly decreased by inosine. The purine also improved lung morphology and suppressed 3-nitrotyrosine staining in the lungs after LPS. Inosine attenuated the cytotoxicity and the expression of IL-8 induced by proinflammatory cytokines in A549 cells. CONCLUSIONS: Inosine largely suppressed LPS-induced lung inflammation in vivo and reduced the toxicity of cytokines in lung cells in vitro. These data support the proposal that inosine might represent a useful adjunct in the therapy of acute respiratory distress syndrome.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Annals of Surgery 235 : 4 (2002), p. 568-578. -
További szerzők:Mabley, Jon G. Pacher Pál Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Soriano, Francisco Garcia Marton Anita Haskó György (1967-) (biokémikus) Deitch, Edwin A. Szabó Csaba (1967-) (orvos)
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6.

001-es BibID:BIBFORM028378
Első szerző:Liaudet, Lucas
Cím:Activation of poly(ADP-Ribose) polymerase-1 is a central mechanism of lipopolysaccharide-induced acute lung inflammation / Lucas Liaudet, Pál Pacher, Jon G. Mabley, László Virág, Francisco G. Soriano, György Haskó, Csaba Szabó
Dátum:2002
ISSN:1073-449X
Megjegyzések:Recent studies demonstrated that activation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) by oxidant-mediated DNA damage is an important pathway of tissue injury in conditions associated with oxidative stress. Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the phenanthridinone PARP inhibitor PJ-34, we now demonstrate an essential role of PARP-1 in the development of pulmonary inflammation induced by lipopolysaccharide (LPS). PARP-1+/+ and PARP-1-/- mice received an intratracheal instillation of LPS (50 microg), followed after 24 h by bronchoalveolar lavage to measure the cytokines TNF-alpha, IL-1beta, and IL-6, the chemokines MIP-1alpha and MIP-2, leukocyte counts and myeloperoxidase activity (neutrophil accumulation), protein content (high permeability edema), and nitrite/ nitrate (nitric oxide production). Malondialdehyde (an index of lipid peroxidation) was measured in lung tissue. Similar experiments were conducted in BALB/c mice treated with PJ-34 or vehicle. The absence of functional PARP-1 reduced LPS-induced increases of cytokines and chemokines, alveolar neutrophil accumulation, lung hyperpermeability, NO production, and lipid peroxidation. Histological analysis revealed attenuated lung damage after PARP inhibition. Our findings support a mechanistic role of PARP-1 in the regulation of LPS-induced lung inflammation. Pharmacological inhibition of PARP may be useful in clinical conditions associated with overwhelming lung inflammation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
lung
ARDS
lipopolysaccharide
poly(ADP-ribose) polymerase
chemokines
külföldön készült közlemény
Megjelenés:American Journal Of Respiratory And Critical Care Medicine 165 : 3 (2002), p. 372-377. -
További szerzők:Pacher Pál Mabley, Jon G. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Soriano, Francisco Garcia Haskó György (1967-) (biokémikus) Szabó Csaba (1967-) (orvos)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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7.

001-es BibID:BIBFORM028376
Első szerző:Liaudet, Lucas
Cím:Flagellin from gram-negative bacteria is a potent mediator of acute pulmonary inflammation in sepsis / Lucas Liaudet, Csaba Szabó, Oleg V. Evgenov, Kanneganti G. Murthy, Pál Pacher, László Virág, Jon G. Mabley, Anita Marton, Francisco G. Soriano, Mikhail Y. Kirov, Lars J. Bjertnaes, and Andrew L. Salzman
Dátum:2003
ISSN:1073-2322
Megjegyzések:Flagellin is a recently identified bacterial product that elicits immune response via toll-like receptor 5. Here, we demonstrate that flagellin is an extraordinarily potent proinflammatory stimulus in the lung during sepsis. In vitro, flagellin triggers the production of interleukin (IL)-8 by human lung epithelial (A549) cells, with 50% of the maximal response obtained at a concentration of 2 x 10(-14) M. Flagellin also induces the expression of ICAM-1 in vitro. Intravenous administration of flagellin to mice elicited a severe acute lung inflammation that was significantly more pronounced than following lipopolysaccharide (LPS) administration. Flagellin induced a local release of proinflammatory cytokines, the accumulation of inflammatory cells, and the development of pulmonary hyperpermeability. These effects were associated with the nuclear translocation of the transcription NF-kappaB in the lung. Flagellin remained active in inducing pulmonary inflammation at doses as low as 10 ng/mouse. In the plasma of patients with sepsis, flagellin levels amounted to 7.1 +/- 0.1 ng/mL. Plasma flagellin levels showed a significant positive correlation with the lung injury score, with the alveolar-arterial oxygen difference as well as with the duration of the sepsis. Flagellin emerges as a potent trigger of acute respiratory complications in gram-negative bacterial sepsis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
endotoxin shock
chemokines
bacterial infection
inflammation
lung
külföldön készült közlemény
Megjelenés:Shock 19 : 2 (2003), p. 131-137. -
További szerzők:Szabó Csaba (1967-) (orvos) Evgenov, Oleg V. Murthy, Kanneganti G. Pacher Pál Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Mabley, Jon G. Marton Anita Soriano, Francisco Garcia Kirov, Mikhail Y. Bjertnaes, Lars J. Salzman, Andrew L.
Internet cím:DOI
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8.

001-es BibID:BIBFORM014260
Első szerző:Liaudet, Lucas
Cím:Protection against hemorrhagic shock in mice genetically deficient in poly(ADP-ribose)polymerase / Liaudet, L., Soriano, F. G., Szabo, E., Virag, L., Mabley, J. G., Salzman, A. L., Szabo, C.
Dátum:2000
ISSN:0027-8424 (Print)
Megjegyzések:Hemorrhagic shock (HS) and resuscitation leads to widespread production of oxidant species. Activation of the enzyme poly(ADP-ribose) polymerase (PARP) has been shown to contribute to cell necrosis and organ failure in various disease conditions associated with oxidative stress. We tested the hypothesis whether PARP activation plays a role in the multiple organ dysfunction complicating HS and resuscitation in a murine model of HS and resuscitation by using mice genetically deficient in PARP (PARP(-/-)) and their wild-type littermates (PARP(+/+)). Animals were bled to a mean blood pressure of 45 mmHg (1 mmHg = 133 Pa) and resuscitated after 45 min with isotonic saline (2x volume of shed blood). There was a massive activation of PARP, detected by poly(ADP-ribose) immunohistochemistry, which localized to the areas of the most severe intestinal injury, i.e., the necrotic epithelial cells at the tip of the intestinal villi, and colocalized with tyrosine nitration, an index of peroxynitrite generation. Intestinal PARP activation resulted in gut hyperpermeability, which developed in PARP(+/+) but not PARP(-/-) mice. PARP(-/-) mice were also protected from the rapid decrease in blood pressure after resuscitation and showed an increased survival time, as well as reduced lung neutrophil sequestration. The beneficial effects of PARP suppression were not related to a modulation of the NO pathway nor to a modulation of signaling through IL-6, which similarly increased in both PARP(+/+) and PARP(-/-) mice exposed to HS. We propose that PARP activation and associated cell injury (necrosis) plays a crucial role in the intestinal injury, cardiovascular failure, and multiple organ damage associated with resuscitated HS.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Acetylcholine/pharmacology
külföldön készült közlemény
Animals
Aorta, Thoracic/drug effects/physiology/physiopathology
Blood Pressure
Blood Volume
Dinoprost/pharmacology
Enzyme Activation
*Hemodynamics
Intestinal Mucosa/enzymology/*pathology
Liver/enzymology/pathology
Male
Mice
Mice, Knockout
Muscle Contraction/drug effects
Muscle Relaxation/drug effects
Muscle, Smooth, Vascular/drug effects/physiology/*physiopathology
Peroxidase/metabolism
Poly(ADP-ribose) Polymerases/deficiency/genetics/*metabolism
Resuscitation
Shock, Hemorrhagic/*genetics/physiopathology/therapy
Sodium Chloride/therapeutic use
Tyrosine/analogs & derivatives/metabolism
Megjelenés:Proceedings of the National Academy of Sciences of the United States of America. - 97 : 18 (2000), p. 10203-10208. -
További szerzők:Soriano, Francisco Garcia Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Mabley, Jon G. Salzman, Andrew L. Szabó Csaba
Internet cím:DOI
elektronikus változat
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM040009
Első szerző:Mabley, Jon G.
Cím:Anti-inflammatory effects of a novel, potent inhibitor of poly (ADP-ribose) polymerase / Mabley, J. G., Jagtap, P., Perretti, M., Getting, S. J., Salzman, A. L., Virág, L., Szabó, É., Soriano, F. G., Liaudet, L., Abdelkarim, G. E., Haskó, G., Marton, A., Southan, G. J., Szabó, C.
Dátum:2001
ISSN:1023-3830
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Inflammation Research. - 50 : 11 (2001), p. 561-569. -
További szerzők:Jagtap, Prakash Perretti, Mauro Getting, S. J. Salzman, Andrew L. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Soriano, Francisco Garcia Liaudet, Lucas Abdelkarim, G. Haskó György (1967-) (biokémikus) Marton, A. Southan, Garry J. Szabó Csaba
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DOI
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10.

001-es BibID:BIBFORM030073
Első szerző:Mabley, Jon G.
Cím:Local and systemic inflammation : role of poly(ADP-ribose) synthetase activation by reactive nitrogen species / Mabley J., Liaudet L., Soriano F. G., Virág L., Jagtap P., Marton A., Lorigados C. B., Gallyas F., Szabo E., Abdulkarim G. E., Hasko G., Southan G. J., Salzman A. L., Szabo C.
Dátum:2001
Tárgyszavak:Orvostudományok Elméleti orvostudományok könyvfejezet
könyvrészlet
Megjelenés:Nitric oxide and inflammation / eds. Salvemini D., Billiar T., Vodovotz Y. - p.
További szerzők:Liaudet, Lucas Soriano, Francisco Garcia Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Jagtap, P. Marton, A. Lorigados, Clara Batista Gallyas Ferenc Jr Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Abdulkarim, G. E. Haskó György (1967-) (biokémikus) Southan, Garry J. Salzman, Andrew L. Szabó Csaba (1967-) (orvos)
Borító:

11.

001-es BibID:BIBFORM014288
Első szerző:Pacher Pál
Cím:Activation of poly(ADP-ribose) polymerase contributes to development of doxorubicin-induced heart failure / Pacher P., Liaudet L., Bai P., Virag L., Mabley J. G., Haskó G., Szabó C.
Dátum:2002
ISSN:0891-5849 (Print)
Megjegyzések:Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) by oxidant-mediated DNA damage is an important pathway of cell dysfunction and tissue injury in conditions associated with oxidative stress. Increased oxidative stress is a major factor implicated in the cardiotoxicity of doxorubicin (DOX), a widely used antitumor anthracycline antibiotic. Thus, we hypothesized that the activation of PARP may contribute to the DOX-induced cardiotoxicity. Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the phenanthridinone PARP inhibitor PJ34, we now demonstrate the role of PARP in the development of cardiac dysfunction induced by DOX. PARP-1+/+ and PARP-1-/- mice received a single injection of DOX (25 mg/kg i.p). Five days after DOX administration, left ventricular performance was significantly depressed in PARP-1+/+ mice, but only to a smaller extent in PARP-1-/- ones. Similar experiments were conducted in BALB/c mice treated with PJ34 or vehicle. Treatment with a PJ34 significantly improved cardiac dysfunction and increased the survival of the animals. In addition PJ34 significantly reduced the DOX-induced increase in the serum lactate dehydrogenase and creatine kinase activities but not metalloproteinase activation in the heart. Thus, PARP activation contributes to the cardiotoxicity of DOX. PARP inhibitors may exert protective effects against the development of severe cardiac complications associated with the DOX treatment.Nitroxyl (NO(-)/HNO), has been proposed to be one of the NO(*)-derived cytotoxic species. Although the biological effect of nitroxyl is largely unknown, it has been reported to cause DNA breakage and cytotoxicity. We have therefore investigated whether NO(-)/HNO-induced DNA single-strand breakage activates the nuclear nick sensor enzyme poly(ADP-ribose) polymerase (PARP) and whether PARP activation affects the mode of NO(-)/HNO- induced cell death. NO(-)/HNO generated from Angeli's salt (AS, sodium trioxodinitrate) (0-300 microM) induced DNA single-strand breakage, PARP activation, and a concentration-dependent cytotoxicity in murine thymocytes. AS-induced cell death was also accompanied by decreased mitochondrial membrane potential and increased secondary superoxide production. The cytotoxicity of AS, as measured by propidium iodide uptake, was abolished by electron acceptors potassium ferricyanide, TEMPOL, the intracellular calcium chelator BAPTA-AM, and by PARP inhibitors 3-aminobenzamide (3-AB) and PJ-34. The cytoprotective effect of 3-AB was paralleled by increased output of AS-induced apoptotic parameters such as phosphatidylserine exposure, caspase activation, and DNA fragmentation. No significant increase in tyrosine nitration could be observed in AS-treated thymocytes as opposed to peroxynitrite-treated cells, indicating that tyrosine nitration is not likely to contribute to NO(-)/HNO-induced cytotoxicity. Our results demonstrate that NO(-)/HNO-induced PARP activation shifts the default apoptotic cell death toward necrosis in thymocytes. However, as total PARP inhibition resulted only in 30% cytoprotection, PARP-independent mechanisms dominate NO(-)/HNO-induced cytotoxicity in thymocytes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Acute Disease
Animals
Antibiotics, Antineoplastic
Creatine Kinase/metabolism
Doxorubicin
Enzyme Activation/drug effects
Heart Failure/ chemically induced/pathology/physiopathology
Hemodynamics/drug effects
L-Lactate Dehydrogenase/metabolism
Male
Metalloendopeptidases/metabolism
Mice
Mice, Inbred BALB C
Mice, Knockout
Poly(ADP-ribose) Polymerases/ genetics/ metabolism
Survival Analysis
Ventricular Function, Left/genetics
Apoptosis
Benzamides/ pharmacology
Caspases/metabolism
Cells, Cultured
DNA Damage/drug effects
DNA Fragmentation/drug effects
Enzyme Activation/drug effects/physiology
Enzyme Inhibitors/ pharmacology
Mice, Inbred C57BL
Mitochondria/ drug effects
Nitrates
Nitrites/toxicity
Nitrogen Oxides/ toxicity
Poly(ADP-ribose) Polymerases/ antagonists & inhibitors/metabolism
Protective Agents/ pharmacology
Thymus Gland/cytology/ drug effects
Tyrosine
Megjelenés:The Journal of Pharmacology and Experimental Therapeutics. - 300 : 3 (2002), p. 862-867. -
További szerzők:Liaudet, Lucas Bai Péter (1976-) (biokémikus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Mabley, Jon G. Haskó György (1967-) (biokémikus) Szabó Csaba
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:

12.

001-es BibID:BIBFORM014261
Első szerző:Pacher Pál
Cím:Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction / Pacher, P., Liaudet, L., Bai, P., Mabley, J. G., Kaminski, P. M., Virag, L., Deb, A., Szabo, E., Ungvari, Z., Wolin, M. S., Groves, J. T., Szabo, C.
Dátum:2003
ISSN:1524-4539 (Electronic)
Megjegyzések:Increased oxidative stress and dysregulation of nitric oxide have been implicated in the cardiotoxicity of doxorubicin (DOX), a commonly used antitumor agent. Peroxynitrite is a reactive oxidant produced from nitric oxide and superoxide in various forms of cardiac injury. Using a novel metalloporphyrinic peroxynitrite decomposition catalyst, FP15, and nitric oxide synthase inhibitors or knockout mice, we now delineate the pathogenetic role of peroxynitrite in rodent models of DOX-induced cardiac dysfunction. METHODS AND RESULTS: Mice received a single injection of DOX (25 mg/kg IP). Five days after DOX administration, left ventricular performance was significantly depressed, and high mortality was noted. Treatment with FP15 and an inducible nitric oxide synthase inhibitor, aminoguanidine, reduced DOX-induced mortality and improved cardiac function. Genetic deletion of the inducible nitric oxide synthase gene was also accompanied by better preservation of cardiac performance. In contrast, inhibition of the endothelial isoform of nitric oxide synthase with N-nitro-L-arginine methyl ester increased DOX-induced mortality. FP15 reduced the DOX-induced increase in serum LDH and creatine kinase activities. Furthermore, FP15 prevented the DOX-induced increase in lipid peroxidation, nitrotyrosine formation, and metalloproteinase activation in the heart but not NAD(P)H-driven superoxide generation. Peroxynitrite neutralization did not interfere with the antitumor effect of DOX. FP15 also decreased ischemic injury in rats and improved cardiac function and survival of mice in a chronic model of DOX-induced cardiotoxicity. CONCLUSIONS: Thus, peroxynitrite plays a key role in the pathogenesis of DOX-induced cardiac failure. Targeting peroxynitrite formation may represent a new cardioprotective strategy after DOX exposure or in other conditions associated with peroxynitrite formation, including myocardial ischemia/reperfusion injury.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Acute Disease
Animals
Catalysis/drug effects
külföldön készült közlemény
Chronic Disease
Creatine Kinase/blood
Disease Models, Animal
Doxorubicin/*toxicity
Enzyme Inhibitors/pharmacology
Heart/*drug effects/physiopathology
Heart Failure/*chemically induced/physiopathology/prevention & control
L-Lactate Dehydrogenase/blood
Male
Metalloporphyrins/*pharmacology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide Synthase/antagonists & inhibitors/genetics/metabolism
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Oxidative Stress/drug effects/genetics
Peroxynitrous Acid/*metabolism
Survival Rate
Megjelenés:Circulation. - 107 : 6 (2003), p. 896-904. -
További szerzők:Liaudet, Lucas Bai Péter (1976-) (biokémikus) Mabley, Jon G. Kaminski, Pawel M. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Deb, Amitabha Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Ungvári Zoltán Wolin, Michael S. Groves, John T. Szabó Csaba
Internet cím:elektronikus változat
Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:
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