Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-inflammatory activity of the IL-1 receptor antagonist, IL-1ra, was evaluated in the acetic acid (HOAc)-induced model of colitis in rats. Animals treated with 10 mg/kg IL-1ra or vehicle were evaluated for general health, acute phase response, and colonic in flammation 24 hours after the initiation of inflammation. A significant decrease in the accumulation of neutrophils in the colonic mucosa as measured by myeloperoxidase activity was seen in animals with HOAc induced colitis that were treated intraperitoneally with IL-1ra when compared to animals with colitis that had been treated with vehicle. IL-1ra also reduced colonic necrosis measured grossly, although there was no effect on the histology IL-1ra had a modest effect on the HOAc-induced acute phase response, as indicated by changes in the serum iron, albumin and transferrin, but the results were not statistically significant. The number of circulating erythrocytes and neutrophils was significantly increased in animals with HOAc-induced colitis and treated with IL-1ra, suggesting that IL-1ra under these experimental conditions inhibited the migration of neutrophils to the injured colon and also the overall intestinal necrosis in the colon as assessed by gross pathology. IL-1ra may be useful as an intestinal anti-inflammatory agent.
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PMID:Evaluation of an interleukin-1 receptor antagonist in the rat acetic acid-induced colitis model. 183 96

The objectives of this study were 1) to quantify the effects of misoprostol (Miso; prostaglandin E1 analogue) on acetic acid-induced increases in mucosal permeability and inflammation; 2) to determine what effect acetic acid, Miso, or the combination of Miso plus acetic acid has on colonic blood flow; and 3) to assess whether the protective effect of Miso may be attributable to its vasodilatory properties. We found that intrarectal administration of acetic acid produced a 6.4-fold increase in colonic myeloperoxidase activity (an index of granulocyte infiltration), an 8.2-fold increase in mucosal permeability, a 1.6-fold increase in colonic weight, and a 6.8% decrease in body weight 48 h after enema. Miso pretreatment significantly attenuated the increases in colonic myeloperoxidase activity, mucosal permeability, and colon weight as well as prevented the loss of body weight. In a different series of experiments, we found that blood flow in the descending, transverse, and ascending colon increased 2.5- to 3.5-fold immediately after the acetic acid enema; however, it returned to control values at 1 and 4 h after enema. Miso pretreatment, followed by acetic acid, resulted in a further increase (2.5-fold) in blood flow in the descending colon 1 h after enema compared with acetic acid alone. This Miso-induced increase in blood flow at 1 h could not account for its protective effect inasmuch as colonic mucosal permeability (i.e., injury) in Miso-pretreated animals was not significantly different from values obtained in animals pretreated with vehicle and then given the enema.
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PMID:Misoprostol attenuates acetic acid-induced increases in mucosal permeability and inflammation: role of blood flow. 190 89

The efficacy of various drugs used to treat ulcerative colitis, (sulfasalazine, 5-aminosalicylate, hydrocortisone) was investigated in a model of acetic acid-induced colitis in the rat. Subsequently, we tested the ability of antioxidant/5-lipoxygenase inhibitors (gossypol and nordihydroguiaretic acid [NDGA]) and a cyclooxygenase inhibitor (indomethacin) to attenuate the macroscopic colonic damage and/or neutrophil influx (myeloperoxidase activity [MPO]) associated with this model of colitis. Oral pretreatment with either sulfasalazine, gossypol, or NDGA significantly decreased colonic MPO activity induced by acetic acid. Intrarectal administration of such drugs resulted in an even larger reduction of the colonic inflammation, with gossypol being the most potent compound. Oral or intrarectal administration of corticosteroids (dexamethasone, hydrocortisone) also attenuated the parameters of acetic acid induced colitis. In contrast, pretreatment with indomethacin was ineffective, or when administered daily after colitis induction, indomethacin actually increased colonic neutrophil influx significantly. Our data suggest that both the route of drug administration and dosing regimen employed affect the antiinflammatory potency and/or efficacy of compounds on colitis induced by acetic acid in the rat. Drugs which were effective against this colitis may act by scavenging of oxygen derived free radicals.
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PMID:Antiinflammatory effects of various drugs on acetic acid induced colitis in the rat. 197 33

Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes ulcerative colitis and Crohn's disease. Leukotriene B4 is thought to be a prominent proinflammatory mediator in these diseases, in that leukotriene B4 levels are increased in the colonic mucosa of inflammatory bowel disease patients and there is increased polymorphonuclear leukocyte infiltration of these tissues. We evaluated the efficacy of 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-3,4-dihydro-8-propyl -2H-1-benzopyran-2-carboxylic acid (SC-41930), a potent, orally active leukotriene B4 receptor antagonist, in a model of inflammatory bowel disease. Colonic mucosal inflammation was induced in rats, guinea pig and rabbits by rectal instillation of a dilute solution of acetic acid. Twenty-four hours later, mucosal levels of myeloperoxidase (a marker enzyme for neutrophil infiltration) and extravasation of i.v. administered Evans blue dye (a marker of vascular disruption and increased permeability) were measured. Tissues were also evaluated histologically. The animals received either SC-41930 or vehicle, intrarectally, 30 min after or 1 hr before and 1 hr after the acetic acid. When given 30 min after acetic acid instillation SC-41930 prevented the rise in myeloperoxidase and dye extravasation observed in the acetic acid inflammed tissue. The SC-41930-treated tissues were less edematous and had fewer neutrophils within the subepithelial space. Median effective dose (ED50) values for vascular protection were approximately 20 mg/kg for both rat and guinea pig. ED50 values for inhibition of granulocyte accumulation were 20 mg/kg for rat, 24 mg/kg for guinea pig and 30 mg/kg for rabbit. These data indicate that SC-41930 is effective locally to prevent acute colonic inflammation.
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PMID:Effect of the leukotriene B4 receptor antagonist SC-41930 on colonic inflammation in rat, guinea pig and rabbit. 217 49

The oxidation of coniferyl alcohol (CA), a lignin precursor, by cell wall peroxidases may take place at the expense of indole-3-acetic acid (IAA) and O2, and in the absence of H2O2. The peroxidase-catalyzed oxidation of CA shows an optimum at an IAA concentration of 0.33 mM, while higher IAA concentrations are inhibitory. The observation that the oxidation of CA by cell wall peroxidase at the expense of IAA and O2 is inhibited by genistein, a putative endogenous inhibitor of lignification in lupin hypocotyls, supports the view that the H2O2-generating system coexists with cell wall peroxidase activities involved in lignification, and that it takes place at the expense of IAA and O2.
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PMID:Oxidation of coniferyl alcohol by cell wall peroxidases at the expense of indole-3-acetic acid and O2. A model for the lignification of plant cell walls in the absence of H2O2. 226 91

The effect of Datura alba (seed) extract on the brain and urinary metabolites of rats was studied. Treatment with Datura brought about a decrease in the activity of brain lipid peroxidase and catalase while an increase in the activity of fructose diphosphate aldolase and glucose 6-phosphate dehydrogenase was observed. An increase in the DNA and RNA contents of brain was noted after the treatment with Datura. The study also showed a marked decrease in the excretion of 5-hydroxyindole acetic acid and vanillyl mandelic acid in the urine of rats given Datura extract.
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PMID:Effect of Datura (seed) on rat brain and urinary metabolites. 243 Feb 65

Singlet oxygen (1 delta g) is a highly reactive, short-lived intermediate which readily oxidizes a variety of biological molecules. The biochemical production of singlet oxygen has been proposed to contribute to the destructive effects seen in a number of biological processes. Several model biochemical systems have been shown to produce singlet oxygen. These systems include the peroxidase-catalyzed oxidations of halide ions, the peroxidase-catalyzed oxidations of indole-3-acetic acid, the lipoxygenase-catalyzed oxidation of unsaturated long chain fatty acids and the bleomycin-catalyzed decomposition of hydroperoxides. Results from these model systems should not be uncritically extrapolated to living systems. Recently, however, an intact cell, the human eosinophil, was shown to generate detectable amounts of singlet oxygen. This result suggests that singlet oxygen may be shown to be a significant biochemical intermediate in a few biological processes.
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PMID:Singlet oxygen production by biological systems. 247 24

Skeletal muscle fibre types were identified by using immunohistochemical detection of sarcoplasmic reticulum Ca2+-ATPase and myoglobin content in rat gastrocnemius muscle. The strong Ca2+-ATPase-reactive fibres were identical with the fast-twitch population, while the fibres with weak reactivity represented the slow-twitch type. Strong myoglobin immunoreactivity reflected the fast oxidative glycolytic (FOG) and slow oxidative (SO) types. Slight to moderate myoglobin immunostaining was found in the fast glycolytic (FG) fibres. The staining intensity of the different fibre types differed as follows: for Ca2+-ATPase FG greater than FOG greater than SO, and for myoglobin FOG greater than SO greater than FG. The immunoreactivity of Ca2+-ATPase and myoglobin were well preserved after fixation of the muscles in Bouin's solution, or in formol/acetic acid fixative, and paraffin embedding. Detection of the primary antibodies was carried out by using the avidin-biotin-peroxidase complex, and the immunogold-silver-staining methods. The latter was found to be more sensitive and suitable for postembedding ultrastructural demonstration of the Ca2+-pump enzyme on Durcupan-embedded muscles. The method, using 5 nm immunogold conjugate with silver enhancement, offered the advantages of high sensitivity and excellent visualization of the reaction product. The postembedding detection of sarcoplasmic reticulum Ca2+-ATPase also proved to be useful in the retrospective identification of the main fibre classes in human muscle biopsies.
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PMID:Fibre typing using sarcoplasmic reticulum Ca2+-ATPase and myoglobin immunohistochemistry in rat gastrocnemius muscle. 252 57

A recently described immunoperoxidase method for the detection of nuclear human cytomegalovirus (HCMV) immediate early antigen (IEA) directly on peripheral blood leucocytes suffers from the drawback that the antigen is vulnerable to endogenous peroxidase inactivation procedures. To solve this problem a procedure is developed in which endogenous peroxidase is inactivated after binding and immobilization of the primary antibody with 4% formaldehyde. In combination with this procedure, three types of inactivation were investigated: glucose/glucose oxidase, hydrochloric acid and methanol/H2O2. Of these three, the first gives optimal results, especially in combination with methanol/acetic acid (20/1 v/v) as the primary fixative. This procedure results in preparations which allow for a more objective evaluation and enable automated examination using bright field microscopy. As a second improvement we developed a simple adherence method in order to diminish the risk of infection for the laboratory staff during processing of unknown blood samples. The protocol described shows great clinical potential for the diagnosis of HCMV infections.
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PMID:An improved immunocytochemical method for the detection of human cytomegalovirus antigens in peripheral blood leucocytes. 254 53

Free oxygen radicals (F.O.R.) belong to a very aggressive chemical species derived from molecular oxygen. Their role in inflammation is well established and Polymorphonuclear neutrophils (PMNS) make use of them as antibacterial weapons. Their role has been experimentally demonstrated in numerous ischemia-reperfusion models. Free radical scavengers such as the superoxide dismutase, allopurinol or desferrioxamine can prevent the occurrence of lesions. The essential role of PMNS in these models is demonstrated by the fact that previous depletion of the animal in PMNS also prevents such lesions. Histologically, in these ischemia-reperfusion models, PMNS infiltration may be quantified by assay of myeloperoxidase. In experimental models of inflammatory colitis (acetic acid, bacterial polysaccharides) intestinal wall infiltration by PMNS is a fundamental phenomenon and is also a characteristic of Crohn's disease and exacerbations of Ulcerative Colitis. Thus, it is probable in both disorders that F.O.R. play an important role since steroids inhibit their secretion by PMNS and 5-aminosalicylic acid has been shown to be a F.O.R. scavenger.
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PMID:[Oxygen free radicals and inflammatory diseases of intestines]. 254 36


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