6533b85afe1ef96bd12b8bc8

RESEARCH PRODUCT

An anti-inflammatory ditriazine inhibiting leukocyte functions and expression of inducible nitric oxide synthase and cyclo-oxygenase-2.

Ricardo RigueraCarlos PeinadorAmalia UbedaMaría Carmen TerencioInmaculada RiojaJ. M. QuintelaL. GonzalezIsabel GuillénMaría José Alcaraz

subject

LipopolysaccharideLeukotriene B4Neutrophilsmedicine.medical_treatmentAnti-Inflammatory AgentsNitric Oxide Synthase Type IICarrageenanNeutrophil Activationchemistry.chemical_compoundMiceLeukocytesEdemaProstaglandin E2biologyPancreatic ElastaseSuperoxideTriazinesHindlimbNitric oxide synthaseIsoenzymesBiochemistryFemalemedicine.drugProstaglandin EBlood PlateletsLeukotriene B4DinoprostonePhospholipases ANitric oxideMicrosomesmedicineAnimalsHumansNitritesPharmacologyInflammationCell-Free SystemDose-Response Relationship DrugZymosanMembrane ProteinsMolecular biologyThromboxane B2chemistryEicosanoidCyclooxygenase 2Prostaglandin-Endoperoxide SynthasesLuminescent Measurementsbiology.proteinMacrophages PeritonealNitric Oxide Synthase

description

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.

10.1016/s0014-2999(00)00243-0https://pubmed.ncbi.nlm.nih.gov/10844115