Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of N-substituted 5H-dibenz[c,e]azepin-5,7(6H)dione, 6-substituted 6,7-dihydro-5H-dibenz[c,e]azepine, 1H-benz[d,e]isoquinoline-1,3(2H)dione and N-benzoyl derivatives was shown to have anti-inflammatory and local analgesic activity in rodents. 6-(4-Chlorophenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated greater than 50% inhibition of induced edema and the writhing reflex at 25 mg/kg, I.P. in mice. 6-Methyl-6,7-dihydro-5H-dibenz[c,e]azepine and the N-butyl and N-pentyl derivatives of the dibenz-[c,e]azepine and N-benzoylbenzamide series demonstrated potent activity in both screens. The 1H-benz[d,e]isoquinoline-1,3(2H)diones were generally less active than the other three chemical classes of agents tested. However, the 2-(methylthio)ethyl derivative of this series demonstrates good activity in both screens. These agents appeared to be as potent as the standards, indomethacin and phenylbutazone, as anti-inflammatory agents in these animal models. Selected agents, e.g. 6-(4-methylphenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated anti-arthritic and anti-gout activities in rodents. The N-methyl and N-butyl derivatives of 6,7-dihydro-5H-dibenz[c,e]azepine afforded good anti-pleurisy activity in rats at 25 mg/kg x 2. The agents which demonstrated potent anti-inflammatory action were found to inhibit acid lysosomal hydrolytic enzyme activities in mouse liver and macrophages at 10(-5) M concentrations. Trypsin, elastase and collagenase activities were also inhibited by the derivatives. Prostaglandin synthetase activity of bovine seminal vesicles and mouse macrophages was inhibited by the compounds at 10(-5) M concentrations.
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PMID:The anti-inflammatory activity of 5H-dibenz[c,e]azepine-5,7(6H)dione, 6,7-dihydro-5H-dibenz[c,e]azepine, N-benzoylbenzamide and 1H-benz[d,e]isoquinoline-1,3(2H)dione derivatives in rodents. 209 97

The intrapleural injection of carrageenin into rats caused accumulation of leucocytes in the pleural cavity and changes in blood leucocyte populations. An increased number of polymorphonuclear (PMN) leucocytes was observed. The peripheral blood PMN leucocytes of untreated rats contained 33.2 nM reduced glutathione/10(7) cells and collagenase mainly in the latent form. During experimental pleurisy in blood leucocytes as well as in the leucocytes obtained from the pleural exudate, the level of reduced glutathione decreased significantly by about 33% (22.4 nM/10(7) cells) and parallel collagenase activation up to 80-100% was observed. Two tested antiinflammatory drugs, Timegadine and piroxicam, which significantly inhibited activation of latent collagenase during the course of inflammation and partially protected reduced glutathione against oxidation. These results suggest that the activation of latent leucocyte collagenase in vivo via the disulphide-thiol interchange reaction may be coupled to the glutathione cycle and regulated by variation in its redox potential.
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PMID:Activation of latent polymorphonuclear leucocyte collagenase by the glutathione cycle. 299 68

Experimental pleurisy induced by carrageenin in rats caused an accumulation of PMN-leukocytes in the pleural cavity and changes in the blood leukocyte population. During the course of the inflammation involved, up to 90-98% activation of latent collagenase was observed in blood PMN-leukocytes and in leukocytes obtained from pleural exudate. The NSAIDs tested for their effect on this process had significant inhibitory effects on both exudate and leukocyte accumulation as well as on the activation of latent collagenase. Timegadine, medosan and sulindac were most effective in preventing collagenase activation, felden and naproxen were less effective, and peroxinorm was without an influence, whereas indomethacin destroyed collagenase activity. These results suggest that the protective effects of NSAIDs against the activation of latent collagenase could be one of their therapeutic actions.
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PMID:Polymorphonuclear leukocyte collagenase in carrageenin-induced inflammation: effect of nonsteroidal antiinflammatory drugs. 301 78

Tenoxicam, a new non-steroidal anti-inflammatory drug has been compared with piroxicam and indomethacin in a range of pharmacological and biochemical inflammation test systems. In a chronic (17-day) adjuvant arthritis in the rat, tenoxicam and piroxicam were equally effective in reducing several indices of inflammation and were less ulcerogenic and better tolerated than indomethacin. The oxicams reduced the oedematous and cellular components of a carrageenan pleurisy at 4 hours while at 24 hours they increased exudate volume and selectively inhibited the accumulation of mononuclear cells. These agents also reduced the inflammatory component of a delayed hypersensitivity response to methylated bovine serum albumin in the mouse. The oxicams were about 100-fold less active than indomethacin as inhibitors of prostaglandin synthetase but all three compounds reduced about equally the release of prostaglandin E2 from phagocytosing rat PMN and interleukin 1-stimulated human rheumatoid synovial cells. The compounds had no effect on the release of superoxide anion, lysosomal enzymes or collagenase from cultured cells, neither did they inhibit isolated collagenase. Only indomethacin stabilized albumin against heat denaturation.
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PMID:Pharmacological and biochemical activities of tenoxicam (Ro 12-0068), a new non-steroidal anti-inflammatory drug. 609 94

Experimental pleurisy in rat and intraperitoneal injection of histamine, serotonin and the histamine releaser compound 48/80 caused changes in blood leucocyte populations. An increased number of PMN-leucocytes was observed. The peripheral blood PMN-leucocytes of non-treated rats contained collagenase mainly in the latent form. During experimental pleurisy and after treatment with histamine, serotonin and compound 48/80 activation of latent collagenase of up to 90-98% was obtained. Mepyramine, cimetidine and timegadine inhibited activation of latent collagenase by compound 48/80. It is suggested that histamine is involved in the process of activation of leucocyte collagenase in the course of inflammation.
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PMID:Histamine, 5-hydroxytryptamine and compound 48/80 activate PMN-leucocyte collagenase of the rat. 632 52

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid-alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61-218) pg x mL(-1) versus 43 (12-83) pg x mL(-1) in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.
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PMID:High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation. 1871 75