title: Effect of sydnone SYD-1 on certain functions of LPS-stimulated macrophages.
abstract: In an earlier article, we demonstrated that sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) inhibits electron transport in the respiratory chain and uncouples oxidative phosphorylation, and postulated that these effects are probably involved in its antitumor activity. We now report the effect of SYD-1 on certain macrophage functions, considering the important role of these cells in inflammatory response and also the relevant anti-inflammatory activity reported for some sydnones. Incubation of macrophages with SYD-1 (5-100 μM) for 48 h did not affect the cell viability up to a concentration of 50 μM. However, at the highest concentration (100 μM), the compound decreased macrophage viability by ~20%. In assays involving 2 h and 24 h of incubation, SYD-1 (5-100 μM) did not affect the cell viability. The incubation of macrophages with the compound for 2 h promoted a dose-dependent reduction of phagocytic activity of up to ~65% (100 μM). SYD-1 (100 μM) was also able to increase the production of superoxide anion (~50%). In the absence of LPS, SYD-1 decreased NO production dose-dependently by up to ~80% (100 μM). When SYD-1 and LPS were incubated concomitantly, the decrease of NO promoted by SYD was the most pronounced, reaching up to ~98% at the same concentration (50 μM). SYD-1 dose-dependently suppressed IL-6 secretion by LPS-stimulated macrophages, reaching up to ~90% of inhibition at the highest concentration (100 μM). These results indicate that SYD-1 promotes effects similar to those described for anti-inflammatory and immunosuppressive drugs, thus motivating further studies to clarify the mechanisms involved in this activity.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Centro Politécnico, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Eduardo Luis
authors.initials: EL
authors.lastname: Bizetto
authors.forename: Guilhermina Rodrigues
authors.initials: GR
authors.lastname: Noleto
authors.forename: Aurea
authors.initials: A
authors.lastname: Echevarria
authors.forename: André Vinicius
authors.initials: AV
authors.lastname: Canuto
authors.forename: Silvia Maria Suter Correia
authors.initials: SM
authors.lastname: Cadena
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007249:Inflammation / Q000139:chemically induced; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
chemical_list: C524256:3-(4-chloro-3-nitrolphenyl)-1,2,3-oxadiazolium-5-olate; D000893:Anti-Inflammatory Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010069:Oxadiazoles; D013481:Superoxides; D009569:Nitric Oxide