An anti-inflammatory ditriazine inhibiting leukocyte functions and expression of inducible nitric oxide synthase and cyclo-oxygenase-2.
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.
Rioja
I
I
Departamento de Farmacología, Universidad de Valencia, Facultad de Farmacia, Av. Vicent Andrés Estellés s/n, 46100 Burjasot, Valencia, Spain.
Ubeda
A
A
Terencio
M C
MC
Guillén
I
I
Riguera
R
R
Quintela
J M
JM
Peinador
C
C
González
L M
LM
Alcaraz
M J
MJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002351:Carrageenan; D002474:Cell-Free System; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D006614:Hindlimb; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008163:Luminescent Measurements; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010196:Pancreatic Elastase / Q000187:drug effects / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*; D015054:Zymosan
C412523:4,10-dichloropyrido(5,6:4,5)thieno(3,2-d')-1,2,3-ditriazine; D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D009573:Nitrites; D014227:Triazines; D007975:Leukotriene B4; D013929:Thromboxane B2; D002351:Carrageenan; D015054:Zymosan; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D010196:Pancreatic Elastase; D015232:Dinoprostone