Comparison of individual and combination treatments with naproxen, prednisolone and hydroxychloroquine to treat Complete Freund’s Adjuvant induced arthritis

Akhtar, Muhammad Furqan (2021) Comparison of individual and combination treatments with naproxen, prednisolone and hydroxychloroquine to treat Complete Freund’s Adjuvant induced arthritis. Inflammopharmacology.

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Abstract

Aim of this study was to evaluate and compare the efficacy of anti-arthritic drugs (naproxen, prednisolone, and hydroxychloroquine)
alone and in combination. The in vitro anti-arthritic activity was evaluated by stabilization of human erythrocytes
(HRBCs) membrane assays. In vivo activity was carried out using Complete Freund’s Adjuvant (CFA) induced arthritic
model in Wistar rat. Individual and combination drugs were administered for 21 days in rats 8 days post inoculation with
CFA (0.15 ml injected in right hind paw). Body weight and paw edema were measured at different intervals. Combination
treatments exhibited more HRBC stabilization than individual treatments. All individual and combination treatments
reduced the level of C-reactive protein (CRP), liver function enzymes, malondialdehyde, white blood cells and platelets,
with the most pronounced activity exhibited by the combination of three drugs. The level of oxidative stress biomarkers
(reduced glutathione, catalase, and superoxide dismutase), red blood cells, and hemoglobin were notably increased in all
treatment groups in contrasts to diseased control rats. Histopathological evaluation of the paw showed that all the treatments
had reduced (p < 0.05–0.001) the arthritic indices in contrasts to diseased control rats. The serum concentrations of TNF-α
and PGE2 were provoked in diseased control rats but had been notably (p < 0.0001) restored by treatments with individual
and combination drugs. It was also found that combination treatments, more precisely triple drug was remarkably effective
in treating arthritis. It can be concluded that naproxen, prednisolone, and hydroxychloroquine effectively ameliorated
the CFA-induced arthritis and were more effective in combination as compared to individual drug therapy probably due
to reduction in oxidative stress and inflammatory markers. Moreover, two lower doses (half NPH/2 and one-third NPH/3)
of triple combination therapy naproxen, prednisolone, and hydroxychloroquine (NPH) showed no significant difference in
anti-arthritic effect as compared to the highest dose level of NPH.

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