English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background  [ 1 , 2 , 4 ] triazolo [4, 3- a ][ 1 , 8 ]naphthyridine derivatives (including NF161 and NF177) were tested for anti-inflammatory, analgesic and antipyretic properties and for their effects on spontaneous locomotor activity in mice and acute gastrolesivity in rats. Both NF161 and NF177 appeared to be anti-inflammatory and analgesic agents without toxic effects or acute gastrolesivity, but NF161 showed stronger anti-inflammatory activity, whereas NF177 was more active as analgesic.    Methods  An EIA kit was used to investigate the ability of NF161 and NF177 to affect prostaglandin E 2  (PGE 2 ) and prostacyclin (PGI 2 ) production by human umbilical vascular endothelial cells (HUVEC).  The compounds' effects on the production of reactive oxygen species (ROS) by human polymorphonuclear cells (PMNs) were studied in an  in vitro  cell model, evaluating inhibition of superoxide anion (O 2  -. ) production induced by  N -formylmethionyl-leucyl-phenylalanine (FMLP). Their effects on PMN adhesion to HUVEC were also investigated; they were incubated with PMNs and endothelial cells (EC) and challenged by stimuli including Platelet Activating Factor (PAF), FMLP, Phorbol Myristate Acetate (PMA), Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β). Adhesion was quantitated by computerized micro-imaging fluorescence analysis.    Results  Neither compounds modified PGE 2  or PGI 2  production induced by IL-1α.  O 2  -.  production and myeloperoxidase release from PMNs stimulated by FMLP was inhibited in a dose- but not time-dependent manner by both [ 1 , 8 ]naphthyridine derivatives, NF161 being statistically more active than NF177 (P < 0.01).  The compounds inhibited adhesion evoked by the pro-inflammatory stimuli PAF, FMLP, TNF-α and IL-1β in a concentration-dependent manner in the 10 -6 –10 -4 M range, being more active when PAF was used as stimulus and inactive when cells were challenged by PMA. Both compounds acted both on PMN and HUVEC.    Conclusion  Considering the interesting anti-inflammatory effects of these compounds in  in vivo  models and the absence of acute gastrolesivity, the study improved knowledge of anti-inflammatory properties of NF161 and NF177, also demonstrating their potential  in vitro , through inhibition of O 2  -.  production, myeloperoxidase release and PMN adhesion to HUVEC. Negative results on PG production suggest a cyclooxygenase (COX)-independent mechanism.

journal of inflammation

Effects of anti-inflammatory [1, 2, 4]triazolo[4, 3-a] [1, 8]naphthyridine derivatives on human stimulated PMN and endothelial cells: an in vitro study