Effect of N-salicyloyltryptamine (STP), a novel tryptamine analogue, on parameters of cell viability, oxidative stress, and immunomodulation in RAW 264.7 macrophages

Cell Biol Toxicol. 2013 Jun;29(3):175-87. doi: 10.1007/s10565-013-9245-2. Epub 2013 Apr 21.

Abstract

Immunomodulatory actions exerted by some classes of tryptamines, such as benzoyltryptamine analogues, suggest these molecules as promising candidates to develop new therapies to treat conditions associated to acute and chronic pain and inflammation. N-salicyloyltryptamine (STP) was observed to act as an anticonvulsive agent and exert antinociceptive effects in mouse. In the present work, we performed a screening of cytotoxic, cytoprotective, immunomodulatory, and redox properties of STP in RAW 264.7 macrophages challenged with hydrogen peroxide and LPS. Our results show that STP presents no cytotoxicity in the range of 0.001 to 1 μg/mL, but doses of 50 and 100 μg/mL caused loss of cell viability (IC(50) = 22.75 μg/mL). Similarly, STP at 0.001 to 1 μg/mL did not cause oxidative stress to RAW 264.7 cells, although it did not prevent cell death induced by H(2)O(2) 0.5 mM. At 1 μg/mL, STP reversed some redox and inflammatory parameters induced by LPS. These include thiol (sulfhydryl) oxidation, superoxide dismutase activation, and morphological changes associated to macrophage activation. Besides, STP significantly inhibited LPS-induced TNF-α and IL-1β release, as well as CD40 and TNF-α protein upregulation. Signaling events induced by LPS, such as phosphorylation of ERK 1/2 and IκBα and p65 nuclear translocation (NF-kB activation) were also inhibited by STP. These data indicate that STP is able to modulate inflammatory parameters at doses that do not interfere in cell viability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Gene Expression Regulation
  • Hydrogen Peroxide / pharmacology
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / immunology
  • Immunomodulation*
  • Inhibitory Concentration 50
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects*
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / immunology
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / immunology
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Oxidative Stress
  • Salicylates / pharmacology*
  • Signal Transduction
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / immunology
  • Tryptamines / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • I-kappa B Proteins
  • Interleukin-1beta
  • Lipopolysaccharides
  • N-salicyloyltryptamine
  • NF-kappa B
  • Nfkbia protein, mouse
  • Salicylates
  • Tryptamines
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Hydrogen Peroxide
  • Superoxide Dismutase
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3