Effect of clopidogrel on the PG-PS-induced arthritis animal model.

<p>(<b>A</b>) Measurements of ankle joint diameter. Values represent the change of paw diameter in millimeters. Changes of paw diameter observed in the PG-PS+clopidogrel group were significantly increased when compare to the PG-PS group from day 15 to day 21, ***<i>p</i><0.0001. (<b>B</b>) Photographic images of paw and ankle joints of the animals on day 5 and day 21.</p

Histology of the ankle joint of the animals.

<p>10× and 40× magnification of paraffin-embedded ankle sections stained with H&E, for the acute phase (day 5) and the chronic phase (day 21). The 40× magnification on day 5 shows leukocyte infiltration in the PG-PS-induced arthritis animals. Slides from the chronic phase in the PG-PS-induced arthritis animals showed fibrosis, pannus formation and severe leukocyte infiltration with more pronounced effects observed in the clopidogrel-treated animals.</p

Complete chemistry profile of experimental animals.

<p>Serum chemistry of rats following clopidogrel treatment in PG-PS-induced arthritis model (day 21). Values are mean ± SD, (n = 6). There are no statistical differences among groups.</p

Platelet aggregation studies using 2MeSADP in PG-PS-induced arthritis model.

<p>Effect of 100 nM of 2MeSADP on platelet aggregation in isolated platelets from untreated animals, clopidogrel-treated animals, PG-PS-induced arthritis animals and PG-PS-induced arthritis+clopidogrel-treated animals. Traces are representative of three independent experiments.</p

Plasma cytokine levels in rats following clopidogrel administration in PG-PS-induced arthritis model (day 21).

<p>Plasma IFN-γ, IL-β and IL-6 levels were elevated in the PG-PS-induced arthritis-treated clopidogrel group. In contrast, plasma levels of IL-10 were significantly lower in the PG-PS-induced arthritis rats compare to the PG-PS-induced arthritis animals alone. Plasma PF4 levels rose in PG-PS-induced arthritis animals (alone and with treatment with clopidogrel; however, no significant differences were observed between these two groups). There were no changes between groups in IL-4 plasma levels. Values represent the mean ± SEM, (n = 4), untreated group (black bar), clopidogrel group (white bar), PG-PS group (light gray bar) and PG-PS treated with clopidogrel group (dark gray bar), * <i>p</i><0.05 PG-PS-induced arthritis group vs. PG-PS-induced arthritis treated with clopidogrel group.</p

Four pathological parameters and the histopathological score from the histological sections of the acute and chronic phases.

<p>Synoviocyte hyperplasia (<b>A</b>), proliferative blood vessels (<b>B</b>), inflammatory infiltrates (<b>C</b>) sub-synovial fibrosis (<b>D</b>) and the histopathological score (<b>E</b>). Values plotted are the mean of the measurements ± SEM, (n = 3 per group) *<i>p</i><0.05, PG-PS-treated with clopidogrel group vs. PG-PS group. Representation of the animals from the untreated and clopidogrel-treated groups was excluded to simplify graphs since these animals showed no inflammatory changes.</p

Blood cell counts of rats following clopidogrel treatment in PG-PS- induced arthritis model.

<p>Leukocyte (<b>A</b>), neutrophil (<b>B</b>), and platelet (<b>C</b>) cell blood counts at day 5 and day 21. All cell blood counts are plotted at 10³/µL. Values are mean ± SEM, (n = 6), untreated group (black bar), clopidogrel group (white bar), PG-PS group (light gray bar) and PG-PS-treated with clopidogrel group (dark gray bar), * <i>p</i><0.05.</p