Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. WY 14643 is a potent PPAR-alpha ligand that modulates the transcription of target genes. The aim of this study was to investigate the effect of WY 14643 on the tissue injury caused by ischemia-reperfusion (I/R) of the gut. I/R injury of the intestine was caused by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed by release of the clamp, allowing reperfusion for 2 h or 4 h. This procedure results in splanchnic artery occlusion (SAO) shock. Rats subjected to SAO developed a significant fall in mean arterial blood pressure, and only 20% of the animals survived for the entire 4-h reperfusion period. Surviving animals were sacrificed for histological examination and biochemical studies. Rats subjected to SAO displayed a significant increase in tissue myeloperoxidase (MPO) activity, significant increases in plasma tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels, and marked injury to the distal ileum. Increased immunoreactivity to nitrotyrosine and polyadenosine diphosphate [ADP]-ribose (PAR) was observed in the ileum of rats subjected to SAO. Staining of sections of the ileum obtained from SAO rats with anti-intercellular adhesion molecule (ICAM-1) antibody or with anti-P-selectin antibody resulted in diffuse staining. Administration of WY 14643 (1 mg/kg i.v.) 30 min before the onset of gut ischemia significantly reduced the (a) fall in mean arterial blood pressure, (b) mortality rate, (c) infiltration of the reperfused intestine with polymorphonuclear neutrophils (MPO activity), (d) production of proinflammatory cytokines (TNF-alpha and IL-1beta), and (e) histological evidence of gut injury. Administration of WY 14643 also markedly reduced the nitrotyrosine formation, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) activation, up-regulation of ICAM-1, and expression of P-selectin during reperfusion. These results demonstrate that the PPAR-alpha agonist WY 14643 significantly reduces I/R injury of the intestine.
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PMID:WY 14643, a potent exogenous PPAR-alpha ligand, reduces intestinal injury associated with splanchnic artery occlusion shock. 1537 89

Hydrogen peroxide (H(2)O(2)) is found in exhaled breath and is produced by airway epithelia. In addition, H(2)O(2) is a necessary substrate for the airway lactoperoxidase (LPO) anti-infection system. To investigate the source of H(2)O(2) produced by airway epithelia, PCR was used to screen nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in human airway epithelia redifferentiated at the air-liquid interface (ALI) and demonstrated the presence of Duox1 and 2. Western blots of culture extracts indicated strong expression of Duox, and immunohistochemistry of human tracheal sections localized the protein to the apical portion of epithelial cells. Apical H(2)O(2) production was stimulated by 100 microM ATP or 1 microM thapsigargin, but not 100 microM ADP. Diphenyleneiodonium, an NADPH oxidase inhibitor, and dimethylthiourea, a reactive oxygen species scavenger, both inhibited this stimulation. ATP did not stimulate the basolateral H(2)O(2) production by ALI cultures. ATP and thapsigargin increased intracellular Ca(2+) with kinetics similar to increasing H(2)O(2) production, and thus consistent with the expected Ca(2+) sensitivity of Duox. These data suggest that Duox is the major NADPH oxidase expressed in airway epithelia and therefore a contributor of H(2)O(2) production in the airway lumen. In addition, the data suggest that extracellular H(2)O(2) production may be regulated by stimuli that raise intracellular Ca(2+).
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PMID:Regulated hydrogen peroxide production by Duox in human airway epithelial cells. 1567 70

Thiazolidinedione rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), are two peroxisome proliferator-activated receptor (PPAR)-gamma ligands. The aim of this study was to investigate the effect of rosiglitazone and 15d-PGJ2 on the lung injury caused by bleomycin administration. Mice subjected to intratracheal administration of bleomycin developed significant lung injury. An increase in immunoreactivity to nitrotyrosine, poly(ADP ribose) polymerase (PARP) and inducible nitric oxide synthase as well as a significant loss of body weight and mortality was observed in the lung of bleomycin-treated mice. Administration of the two PPAR-gamma agonists rosiglitazone (10 mg x kg(-1) i.p.) and 15d-PGJ2 (30 microg x kg(-1) i.p.) significantly reduced the: 1) loss of body weight, 2) mortality rate, 3) infiltration of the lung with polymorphonuclear neutrophils (myeloperoxidase activity), 4) oedema formation, and 5) histological evidence of lung injury. Administration of rosiglitazone and 15d-PGJ2 also markedly reduced the nitrotyrosine, PARP and inducible nitric oxide synthase formation. In addition, treatment with the PPAR-gamma antagonist bisphenol A diglycidyl ether (1 mg x kg(-1) i.p. 30 min before the rosiglitazone or 15d-PGJ2) significantly antagonised the effect of the two PPAR-gamma agonists. These results demonstrate that the two peroxisome proliferator-activated receptor-gamma agonists, rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2, significantly reduce lung injury induced by bleomycin in mice.
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PMID:Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury. 1568 85

The immunological and genetic pathogeneses of inflammatory bowel disease (IBD) have been well studied but not well elucidated in the recent years. Accordingly, the pharmacological treatment of IBDs is focusing upon the individual pathologic step (targeting therapy). It has been shown recently that new drugs such as biological immunomodulating agents and anti-inflammatory cytokines have better short-term effects in some respects than the conventional drugs, and they might change the treatment strategy of IBDs in the near future. The aim of the present study was to examine the effects of thalidomide treatment in the development of experimental colitis. To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). DNBS-treated mice experienced diarrhea and weight loss. At 4 days after administration of DNBS, the mucosa of the colon exhibited large areas of necrosis. The observed mucosa alteration was associated with the colon production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and vascular endothelial growth factor (VEGF). Neutrophil infiltration (determined by histology as well as an increase in myeloperoxidase activity in the mucosa) was associated with an upregulation of intercellular adhesion molecule-1. Immunohistochemistry for nitrotyrosine and poly (ADP ribose) showed an intense staining in the inflamed colon. When compared with DNBS-treated mice, thalidomide-treated (200 mg/kg orally) mice subjected to DNBS-induced colitis experienced a significantly lower rate in the extent and severity of the histological signs of colon injury. Thalidomide also caused a substantial reduction of the rise in myeloperoxidase activity (mucosa), in the increase in the tissue levels of TNF-alpha, IL-1beta, and VEGF, in the increase in staining (immunohistochemistry) for nitrotyrosine and for poly (ADP ribose), as well as in the upregulation of intercellular adhesion molecule-1 caused by DNBS in the colon. Thus, thalidomide treatment reduces the degree of colitis caused by DNBS. We propose that this evidence may help to clarify the therapeutic actions of thalidomide in patients with Crohn's disease.
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PMID:Thalidomide treatment reduces colon injury induced by experimental colitis. 1589 10

Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants, and/or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidative stress and exaggerated production of reactive oxygen species play a major role in several aspects ischemia and reperfusion. Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. Because polyphenolic compounds have high antioxidant potential, in this study we evaluated the effect of H. perforatum extract on splanchnic artery occlusion (SAO) shock-mediated injury. SAO shock was induced in rats by clamping the superior mesenteric artery and the celiac trunk for 45 min. After 1 h of reperfusion, SAO-shocked rats developed a significant fall in mean arterial blood pressure. Treatment of rats with H. perforatum extract (applied at 25 mg/kg 15 min before reperfusion) significantly reduced a significant fall in mean arterial blood pressure and the migration of polymorphonuclear cells caused by SAO-shock. H. perforatum extract also attenuated the ileum injury (histology) as well as the increase in the tissue levels of myeloperoxidase and malondialdehyde caused by SAO shock in the ileum. Immunohistochemical analysis for nitrotyrosine and for poly ADP-ribosylated proteins revealed a positive staining in ileum from SAO-shocked rats. The degree of staining for nitrotyrosine and poly ADP-ribosylated proteins was markedly reduced in tissue sections obtained from SAO-shocked rats that had received H. perforatum extract. Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin and for intercellular adhesion molecule-1 in the vascular endothelial cells. H. perforatum extract treatment markedly reduced the intensity and degree of P-selectin and intercellular adhesion molecule-1 in tissue section from SAO-shocked rats. H. perforatum extract treatment significantly improved survival. In conclusion, this study demonstrates that H. perforatum extract exerts multiple protective effects in splanchnic artery occlusion-reperfusion shock and suggests that H. perforatum extract may be a candidate for consideration as a therapeutic intervention for ischemia-reperfusion injury.
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PMID:Effects of Hypericum perforatum extract in a rat model of ischemia and reperfusion injury. 1613 65

Herein we are presenting the clinical, morphological and cytochemical characteristics of five cases of acute megakaryoblastic leukaemia (AML-M7) seen by us over a period of five years (Jan 1996-Dec 2000). Morphological assessment revealed marked polymorphism of blast cells and platelets both in the peripheral blood and bone marrow smears in all cases. Size of the blast cells ranged from very small to very large multinucleated cells, with variable chromatin pattern and number of nucleoli. More differentiated megakaryocytic cells showing cytoplasmic blebs, protrusions and platelet budding with bizarre platelet morphology were characteristic features suggesting the diagnosis. Cytochemical stains like myeloperoxidase, sudan black and PAS were positive in 5-15% of blast cell. Coagulation studies revealed a normal coagulation profile, whereas platelet studies showed marked impairment in aggregation of platelets with ADP and adrenalin with a normal PF-3 availability.
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PMID:Acute megakaryoblastic leukaemia: a clinico-haematological profile of five cases. 1629 95

1. Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and inflammation which contribute to the pathophysiology of shock. We investigated the effects of relaxin (RLX), known to afford protection against the deleterious effects of cardiac ischemia/reperfusion, given to rats subjected to splanchnic artery occlusion and reperfusion (SAO/R)-induced splanchnic injury. 2. RLX (30 ng kg(-1), 15 min. before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/R. RLX also reduced histopathological changes, leukocyte infiltration (myeloperoxidase) and expression of endothelial cell adhesion molecules in the ileum. RLX counteracted free radical-mediated tissue injury, as judged by significant decrease in the tissue levels of peroxidation and nitration products (malondialdehyde, nitrotyrosine), DNA damage markers (8-hydroxy-2'-deoxyguanosine, poly-ADP-ribosylated DNA) and consumption of tissue antioxidant enzymes (superoxide dismutase). As a result, RLX led to a reduction of ileal cell apoptosis (caspase 3, terminal deoxynucleotidyltransferase-mediated UTP end labeling). The effects of RLX appear specific, as inactivated RLX substituted for the bioactive hormone had no effects. 3. In conclusion, these results show that RLX exerts a clear-cut protective effect in SAO/R-induced splanchnic injury, likely due to endothelial protection, decreased leukocyte recruitment and hindrance of free radical-mediated tissue injury leading to cell death, lethal complications and high mortality rate. Thus, RLX could be used therapeutically in intestinal ischemia.
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PMID:Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion. 1684 43

The pro-oxidant activities of baicalein, morin, myricetin, quercetin, and rutin were examined in various cell-containing systems including human platelets, rat vascular smooth muscle cells, human umbilical vein endothelial cells (HUVECs), human THP-1 cells, and fibroblast cells. Electron spin resonance (ESR) results showed that only baicalein generated hydroxyl radicals in a resting human platelet suspension, whereas the other flavonoids showed no effects on any of the resting cell systems. A low concentration of arachidonic acid (AA) increased the intensity of hydroxyl radicals, but a high concentration inhibited it. Collagen and thrombin, platelet aggregatory agents that can cause the release of AA by platelets, enhanced baicalein-induced hydroxyl radical formation, whereas ADP and U44619 showed no significant effects. Quinacrine and 5,8,11,14-eicosatetraenoic trifluoromethyl ketone, both PLA2 inhibitors, significantly attenuated baicalein-induced hydroxyl radical formation. These results suggest that baicalein-induced hydroxyl radical formation is associated with AA metabolite enzymes in human platelets. The formation of hydroxyl radicals was significantly inhibited by lipoxygenase inhibitors including nordihydroguaiaretic acid, (-)-epicatechin, (-)-epicatechin gallate, and hinokitiol, but was not affected by desferroxamine or the heme protein inhibitors KCN and NaN3. On the other hand, semiquinone free radicals were generated when baicalein was incubated with horseradish peroxidase/H2O2 or platelets/AA. The semiquinone radicals formed in the platelets/AA system could be extensively inhibited by desferroxamine, diethylenetriaminepentaacetic acid, KCN, and NaN3, indicating that prostaglandin H synthase (PGHS)-peroxidase may be involved. The results of this study led to the proposal that baicalein induces hydroxyl radical formation via 12-lipoxygenase and induces semiquinone radical formation via PGHS-peroxidase in human platelets.
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PMID:Baicalein induction of hydroxyl radical formation via 12-lipoxygenase in human platelets: an ESR study. 1726 56

Poly(ADP-ribose) polymerases (PARP) comprise a family of enzymes which catalyse poly(ADP-ribosyl)ation of DNA-binding proteins. Multiple researches indicate the importance of PARP in promoting cell recruitment and thereby inducing organ injury in various forms of inflammation, such as colitis. We have evaluated the effects of two PARP inhibitors, nicotinamide and 1,5-dihydroxyisoquinoline, in acute colitis induced by trinitrobenzensulfonic acid (TNBS) in rats. Nicotinamide (20-40 mg/kg) and 1,5-dihydroxyisoquinoline (4-8 mg/kg) were administered 48, 24 and 1 h prior to the induction of colitis as well as 24 h later. 48 h after colitis induction the lesions were blindly scored and quantified as ulcer index. Histological study and colonic inflammation were assessed by gross appearance and myeloperoxidase (MPO) activity. Prostaglandin E2 (PGE2) synthesis and, cyclooxygenase-1 and cyclooxygenase-2 expressions by Western blotting and immunohistochemistry were also performed. Inflammation following TNBS induction was characterized by increased colonic wall thickness, oedema, diffuse inflammatory cells infiltration in the mucosa and necrosis. Furthermore, increased MPO activity, cyclooxygenase-2 expression and PGE2 synthesis were significantly augmented after TNBS instillation. On the contrary, treatment with 1,5-dihydroxyisoquinoline significantly reduced the degree of colon injury and also caused a substantial reduction in the rise in MPO activity, in the increase of staining for cyclooxygenase-2, as well as in the up-regulation of PGE2 caused by TNBS in the colon. Although nicotinamide significantly did not reduce macroscopic damage, it decreased both MPO activity and PGE2 colonic levels. In conclusion, we demonstrated that PARP inhibition can exert beneficial effects in experimental colitis and may, therefore, be useful in the treatment of ulcerative colitis.
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PMID:PARP inhibition reduces acute colonic inflammation in rats. 1737 31

In this study, the involvement of 5-HT2A receptors on mesenteric ischemia-reperfusion injury was examined in mice. Intestinal ischemia produced by 45 min occlusion of superior mesenteric artery was followed by 24h reperfusion (I/R). The 5-HT2A selective antagonist, ketanserin (0.5 mgkg(-1)) or the 5-HT2A agonist DOI (0.25 mgkg(-1)) was intravenously administered before ischemia and 8h after the beginning of reperfusion. The effects were compared with those obtained in sham operated animals (S). Ketanserin prevented the upper gastrointestinal transit delay induced by I/R (P<0.01), protected intestine from leukocyte recruitment as indicated by jejunal myeloperoxidase activity (P<0.05) and reverted Evans Blue extravasation elicited by I/R in lung, colon and jejunum (P<0.05). On the other hand, 5-HT2A activation by DOI mimicked the effects of I/R in S mice prolonging small intestine transit (P<0.05) and enhancing neutrophil accumulation in jejunal tissues (P<0.05). Furthermore, the reduction of ADP-induced platelet aggregation in plasma of I/R mice was prevented by ketanserin treatment. All together, these findings support the critical involvement of 5-HT2A receptor subtype in mediating the damage induced by mesenteric I/R in mice.
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PMID:Evidence for the involvement of 5-HT2A receptors in mild mesenteric ischemia/reperfusion dysfunctions in mice. 1802 56


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