ISSN:
1437-160X
Keywords:
Active center analogues of superoxide dismutase
;
Collagen type II-induced arthritis
;
Potassium peroxochromate arthritis
;
Autoimmunity
;
Chemiluminescence
;
Inhibition of tumor necrosis factor alpha
;
Reactive oxygen species
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The anti-arthritic and anti-inflammatory efficacy of CuPu(Py)2 {[N, N′-bis(2-pyridylmethylene)-1,4-butanediamine] (N, N′, N″, N‴)}-Cu(II), a serum-stable active center analogue of Cu2Zn2-superoxide dismutase (SOD; EC 1.15.1.1), was tested in male DBA/1xB10A (4R) mice suffering from potassium-peroxochromate-induced (PIA) or collagen type II-induced arthritis (CIA). Parameters including the arthritis index, the plasma SOD activity, and the inhibition of phagocytic responses in unseparated blood were used for the assessment of disease activity. A dose-dependent suppression of arthritis was noted in both models. The ED50 was 2.5±0.4 μmol/kg/day of CuPu(Py)2 for PIA and 4.0±1.1 μmol/kg/day for CIA. The arthritis index correlated with both the levels of reactive oxygen species (ROS) generated by phorbol ester-activated neutrophils and monocytes in unseparated blood (r=0.892) and the SOD-like activity in plasma (r=0.857). CuPu(Py)2 inhibited also the lipoplysaccharide-induced release of tumor necrosis factor alpha from human monocytes and neutrophils in a dose-dependent manner. Unlike SOD, which exerts successful anti-rheumatic activity mainly upon intra-articular injection, the SOD-mimic CuPu(Py)2 can be applied systemically. Non-proteinaceous low molecular weight antioxidases may well be suited to control oxidative stress-derived damage in rheumatic diseases by modulation of ROS-dependent signal transduction pathways.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00300814
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