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 effects of ketotifen, a 'mast cell stabiliser,' on two models of experimental colitis were examined. The inflammatory response elicited by either trinitrobenzene sulphonic acid or acetic acid resulted in increased colonic synthesis of platelet activating factor, prostaglandin E2, thromboxane B2, leukotrienes B4 and C4, and myeloperoxidase activity. Intragastric administration of ketotifen 100 micrograms/100 grams twice daily significantly decreased mucosal damage when given prophylactically 48 hours before the induction of colitis and then throughout the experiment. This effect was consistent in both models and was accompanied by a significant reduction in mucosal generation of platelet activating factor, prostaglandin E2, thromboxane B2, and leukotrienes C4 and B4. Myeloperoxidase activity was reduced as well, reaching significance only in the acetic acid model. This study shows that both trinitrobenzene sulphonic acid and acetic acid colitis can be pharmacologically manipulated by ketotifen. The mechanism of action of ketotifen has not yet been determined. Ketotifen's potential in the treatment of active inflammatory bowel disease or in the prevention of exacertations, or both, remains to be elucidated.
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PMID:Ketotifen effectively prevents mucosal damage in experimental colitis. 145 75

We examined the effects of Y-24180, a potent and long-acting antagonist to platelet-activating factor (PAF), on allergic cutaneous eosinophilia and cytokine production in the skin of mice. Mice sensitized actively with ovalbumin (OA) were challenged by an intradermal injection of OA solution. The number of inflammatory cells, including eosinophils and eosinophil peroxidase (EPO) activity reflecting eosinophil infiltration into the tissue increased in OA-challenged skin 12 hr after the challenge. The levels of interleukin-4 (IL-4) and IL-5 also increased significantly in the challenged skin 12 hr and 3-24 hr, respectively, but that of interferon-gamma (IFN-gamma) did not change. Then, we evaluated the effects of Y-24180, ketotifen, suplatast and prednisolone on the increase in EPO activity, IL-4 and IL-5. These drugs were orally administered once a day for 5 days beginning 4 days before the challenge. Y-24180 (10 mg/kg) and prednisolone (5 mg/kg) significantly suppressed these parameters. Suplatast did not affect EPO activity, but significantly decreased the levels of IL-4 and IL-5. Ketotifen had no effect on them. These results indicate that the inhibition of IL-4, IL-5 and PAF are required to suppress the cutaneous eosinophilia and Y-24180 contributes to the treatment of allergic cutaneous eosinophilia.
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PMID:Effects of Y-24180, a receptor antagonist to platelet-activating factor, on allergic cutaneous eosinophilia in mice. 1020 47

Ketotifen was used as an anti-allergic agent to study the relationship between eosinophil-related responses and IgG1 and IgG2a antibody responses in BALB/c mice infected with Trichinella spiralis. The results showed that leukocyte and eosinophil numbers and interleukin-5 (IL-5) concentrations in the peritoneal fluid increased after exposure to nematodes and the increases were slightly greater in animals treated with ketotifen. A decreased concentration of eosinophil peroxidase and an elevation in IgG1 accompanied the muscle phase of infection. In mice treated with ketotifen, antibody-mediated recognition of muscle larvae was delayed. The retardation of IgG1 and IgG2a responses may have been responsible for the ineffective immune response against larvae migrating into the muscle. The activation of eosinophils was accompanied by changes in IL-5 concentration, but these changes were not associated with differences in protection against infection.
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PMID:Immune response to Trichinella spiralis larvae after treatment with the anti-allergic compound ketotifen. 1072 94

The protective action of zinc compounds in Crohn's disease-like inflammatory bowel disease in animals has been shown. A similar action of zinc sulfate on ulcerative colitis has not been defined. The present study aimed to delineate the protective action of zinc sulfate and the pathogenic mechanisms of 2,4-dinitrobenzene sulfonic acid (DNBS)-induced ulcerative colitis in rats. Zinc sulfate at different concentrations was given either orally (p.o.) or rectally (p.r.) to rats at 42, 48, 66 and 72 h following the induction of colonic inflammation by DNBS. Rats were killed 96 h after instillation of DNBS rectally to assess the severity of colonic damage, myeloperoxidase and xanthine oxidase activities. The involvement of mast cell degranulation and histamine release in the pathogenesis of DNBS-induced colitis was determined by using a mast cell stabilizer (ketotifen) and histamine receptor blockers (terfenadine and ranitidine). DNBS given rectally produced inflammation and ulceration in rats with a pathology resembling ulcerative colitis. Myeloperoxidase activity but not xanthine oxidase activity was sharply increased by this agent. Intrarectal administration of zinc solution and parenteral injection of histamine blockers significantly reduced tissue damage and myeloperoxidase but not xanthine oxidase activity. Ketotifen, a mast cell stabilizer, also significantly decreased mucosal injury and myeloperoxidase activity in the colon. In conclusion, mast cell degranulation followed by histamine release plays an important role in the pathogenesis of DNBS-induced ulcerative colitis. Zinc given rectally has a therapeutic effect against this colitis model, perhaps through the reduction of inflammation and inhibition of the above pathogenic mechanisms.
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PMID:Delineation of the protective action of zinc sulfate on ulcerative colitis in rats. 1204 10

This study was designed to investigate the cardioprotective effects of pharmacological interventions, modulating resident cardiac mast cells, on ischemia-reperfusion-induced injury. Isolated rat hearts were mounted on Langendorff apparatus and subjected to 30-min global ischemia followed by 120-min reperfusion. The extent of mast cell degranulation was assessed by release of mast cell peroxidase (MPO). The release of lactate dehydrogenase (LDH) and creatine kinase (CK) and estimation of infarct size were used to assess the extent of myocardial injury. Left ventricle developed pressure (LVDP) and its derivatives, that is, dp/dt(max) and dp/dt(min), were recorded to evaluate the postischemic recovery of the contractility of heart. Ketotifen (0.1 microM) and low-dose carvedilol (0.1 microM), without beta-blockade activity, attenuated ischemia-reperfusion-induced mast cell degranulation along with the reduction in myocardial injury, suggesting the protective effects of mast cell stabilization during ischemia and reperfusion. Administration of compound 48/80 (1 microg/ml), a specific mast cell degranulating agent, completely degranulated cardiac mast cells before global ischemia. Moreover, it also resulted in the attenuation of ischemia-reperfusion-induced myocardial injury. Decreased release of cytotoxic mediators from already degranulated (empty) mast cells during sustained global ischemia may be responsible for the cardioprotective effects of compound 48/80. Administration of carvedilol or ketotifen after compound 48/80 perfusion did not further enhance the cardioprotective effects, suggesting that the cardiac mast cells may be the common target site for ketotifen, compound 48/80 and low-dose carvedilol.
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PMID:Cardioprotective effects of mast cell modulators in ischemia-reperfusion-induced injury in rats. 1819 10

Eosinophils play a major role in the development and severity of asthma. Robust and rapid preclinical animal models are desirable to profile novel therapeutics inhibiting the influx of eosinophils into the airways. To develop a rapid, airway eosinophil recruitment model in the rat, Brown-Norway (BN) rats were immunised with ovalbumin (OVA)/alum on day 0, 1 and 2 and challenged with OVA aerosol on day 5 and 6. On day 7 bronchoalveolar lavage fluid (BALF) was analysed for eosinophil numbers, eosinophil peroxidase (EPO) activity and cytokines. Lung sections were also examined. The immunised animals showed a strong selective influx of eosinophils into the airways correlating with enhanced EPO activity, Interleukin (IL-4), IL-5 and monocytes chemo attractant protein levels in the BALF in comparison to sham-sensitised rats. In addition the immunised rats developed goblet cell metaplasia in the lung and showed OVA specific IgG1 and IgE levels in the serum but no airway hyperreactivity after metacholine challenge. Airway inflammation was suppressed by applying the steroids Budesonide (intra tracheally) and Prednisolone (per orally), Roflumilast a phosphodiesterase-4 inhibitor, and the H1 receptor antagonists Epinastine and Ketotifen. Montelukast, a Leukotriene receptor antagonist and Chromoglycate, a mast cell stabiliser, had no effect in this model. In summary, in this novel preclinical rat model therapeutics expected to inhibit the development of airway eosinophilia can rapidly be tested.
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PMID:Development and characterisation of a novel and rapid lung eosinophil influx model in the rat. 1849 Jan 84