Monosodium urate crystals (MSU) deposition induces articular
inflammation known as
gout. This disease is characterized by intense articular
inflammation and
pain by mechanisms involving the activation of the
transcription factor NFκB and
inflammasome resulting in the production of
cytokines and oxidative stress. Despite evidence that MSU induces iNOS expression, there is no evidence on the effect of
nitric oxide (NO) donors in
gout. Thus, the present study evaluated the effect of the
ruthenium complex donor of NO {[
Ru(bpy)2(NO)SO3](PF6)} (complex I) in
gout arthritis. Complex I inhibited in a dose-dependent manner MSU-induced
hypersensitivity to mechanical stimulation,
edema and leukocyte recruitment. These effects were corroborated by a decrease of histological
inflammation score and recruitment of Lysm-eGFP+ cells. Mechanistically, complex I inhibited MSU-induced mechanical
hypersensitivity and joint
edema by triggering the cGMP/PKG/
ATP-sensitive K (+) channels signaling pathway. Complex I inhibited MSU-induced oxidative stress and pro-inflammatory
cytokine production in the knee joint. These data were supported by the observation that complex I inhibited MSU-induced NFκB activation, and IL-1β expression and production. Complex I also inhibited MSU-induced activation of pro-IL-1β processing. Concluding, the present data, to our knowledge, is the first evidence that a NO donating
ruthenium complex inhibits MSU-induced articular
inflammation and
pain. Further, complex I targets the main physiopathological mechanisms of
gout arthritis. Therefore, it is envisaged that complex I and other NO donors have therapeutic potential that deserves further investigation.