Abstract
A ditriazine derivative (4,10-dichloropyrido[5,6:4,5]thieno[3,2-d':3, 2-d]-1,2,3-ditriazine (DTD)) inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B(4) production, without any effect on 5-lipoxygenase activity. This compound reduced nitric oxide (NO) and prostaglandin E(2) production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase, cyclo-oxygenase-2 or cyclo-oxygenase-1 was observed. DTD significantly reduced mouse paw oedema induced by carrageenan and also markedly reduced NO and prostaglandin E(2) levels in exudates from 24-h zymosan-stimulated mouse air pouch. Western blot analysis showed that DTD reduced the expression of inducible NO synthase and cyclo-oxygenase-2. Our results indicate that DTD exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E(2) production, which could be due to a decreased expression of inducible NO synthase and cyclo-oxygenase-2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Blood Platelets / drug effects
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Blood Platelets / metabolism
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Carrageenan
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Cell-Free System
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Cyclooxygenase 2
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Dinoprostone / metabolism
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Dose-Response Relationship, Drug
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Edema / chemically induced
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Edema / metabolism
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Edema / prevention & control
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Female
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Hindlimb
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Humans
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Inflammation / chemically induced
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Inflammation / metabolism
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Inflammation / prevention & control
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Isoenzymes / drug effects*
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Isoenzymes / metabolism
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Leukocytes / cytology
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Leukocytes / drug effects*
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Leukocytes / metabolism
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Leukotriene B4 / metabolism
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Luminescent Measurements
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / enzymology
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Macrophages, Peritoneal / metabolism
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Membrane Proteins
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Mice
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Microsomes / drug effects
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Microsomes / metabolism
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Neutrophil Activation / drug effects
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Neutrophils / drug effects
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Neutrophils / enzymology
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Neutrophils / metabolism
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Nitric Oxide Synthase / drug effects*
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type II
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Nitrites / metabolism
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Pancreatic Elastase / drug effects
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Pancreatic Elastase / metabolism
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Phospholipases A / metabolism
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Prostaglandin-Endoperoxide Synthases / drug effects*
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Prostaglandin-Endoperoxide Synthases / metabolism
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Thromboxane B2 / metabolism
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Triazines / chemistry
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Triazines / pharmacology*
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Zymosan
Substances
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4,10-dichloropyrido(5,6:4,5)thieno(3,2-d')-1,2,3-ditriazine
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Anti-Inflammatory Agents
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Isoenzymes
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Membrane Proteins
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Nitrites
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Triazines
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Leukotriene B4
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Thromboxane B2
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Carrageenan
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Zymosan
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NOS2 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Phospholipases A
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Pancreatic Elastase
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Dinoprostone