TY - JOUR
T1 - The anti-inflammatory and antinociceptive effects of NF-κB inhibitory guanidine derivative ME10092
AU - Dambrova, Maija
AU - Zvejniece, Liga
AU - Skapare, Elina
AU - Vilskersts, Reinis
AU - Svalbe, Baiba
AU - Baumane, Larisa
AU - Muceniece, Ruta
AU - Liepinsh, Edgars
N1 - Funding Information:
This work was supported by grants from the Taiho Latvia Foundation , by the ES Foundation ( ESS 2004/3 ) and by the L'Oréal Latvian fellowship “For Women in Science” with the support of the Latvian National Commission for UNESCO and the Latvian Academy of Sciences .
PY - 2010/4
Y1 - 2010/4
N2 - The guanidine compound ME10092 (1-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine) is known to possess anti-radical and anti-ischemic activity but its molecular targets have not been identified. This study investigated whether ME10092 regulates the nuclear factor kappa B (NF-κB)-mediated signal transduction in vivo. The effect of ME10092 treatment (1-100 pmol/mouse) on nuclear translocation of NF-κB, activation of expression of inflammatory mediators and production of nitric oxide were measured in the lipopolysaccharide (LPS)-induced brain inflammation model in mice in vivo. The antinociceptive activity of ME10092 was tested in the formalin-induced paw licking test. ME10092 dose-dependently inhibited LPS-induced nuclear translocation of NF-κB, transcription of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Electron paramagnetic resonance measurements showed that ME10092 inhibited the LPS-induced increase in nitric oxide content in mouse brain tissue in a dose-dependent manner. In the formalin-induced paw licking test, ME10092 (at the dose of 3 mg/kg, p.o. twice daily for eight days) significantly reduced nociceptive response. In conclusion, above results indicate that ME10092 inhibits NF-κB activation and suppresses the up-regulation of inflammatory mediators in experimental models in vivo.
AB - The guanidine compound ME10092 (1-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine) is known to possess anti-radical and anti-ischemic activity but its molecular targets have not been identified. This study investigated whether ME10092 regulates the nuclear factor kappa B (NF-κB)-mediated signal transduction in vivo. The effect of ME10092 treatment (1-100 pmol/mouse) on nuclear translocation of NF-κB, activation of expression of inflammatory mediators and production of nitric oxide were measured in the lipopolysaccharide (LPS)-induced brain inflammation model in mice in vivo. The antinociceptive activity of ME10092 was tested in the formalin-induced paw licking test. ME10092 dose-dependently inhibited LPS-induced nuclear translocation of NF-κB, transcription of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Electron paramagnetic resonance measurements showed that ME10092 inhibited the LPS-induced increase in nitric oxide content in mouse brain tissue in a dose-dependent manner. In the formalin-induced paw licking test, ME10092 (at the dose of 3 mg/kg, p.o. twice daily for eight days) significantly reduced nociceptive response. In conclusion, above results indicate that ME10092 inhibits NF-κB activation and suppresses the up-regulation of inflammatory mediators in experimental models in vivo.
KW - Brain inflammation
KW - Formalin-induced paw licking test
KW - Lipopolysaccharide
KW - Nitric oxide
KW - Nuclear factor kappa B
UR - http://www.scopus.com/inward/record.url?scp=77949487187&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2010.01.006
DO - 10.1016/j.intimp.2010.01.006
M3 - Article
C2 - 20074673
AN - SCOPUS:77949487187
SN - 1567-5769
VL - 10
SP - 455
EP - 460
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 4
ER -