Original article

Comparative effects of topically applied diclofenac, ketoprofen, and piroxicam on interleukin-17, signal transducer and activator of transcription 3, and prostaglandin E2 levels in a rat model of collagen-induced arthritis

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Abstract

Aim: To evaluate and compare the effects of topically applied diclofenac, ketoprofen, and piroxicam on key inflammatory mediators, including interleukin-17 (IL-17), prostaglandin E2 (PGE2), and signal transducer and activator of transcription 3 (STAT3), in a rat model of collagen-induced arthritis (CIA).

Methods: Thirty male Wistar rats were assigned to five groups: three experimental groups receiving topical diclofenac, ketoprofen, or piroxicam, respectively, a positive control group receiving a placebo patch, and a negative control group without collagen injection. CIA was induced using bovine type II collagen and incomplete Freund’s adjuvant, with arthritis severity assessed through macroscopic scoring. NSAID patches were applied to the right hind paw for 6 hours daily over 5 days. Immunological parameters were quantified via enzyme-linked immunosorbent assay (ELISA). Statistical analysis included ANOVA, Kruskal-Wallis, and mixed-effects models to evaluate drug effects over time.

Results: A significant difference was observed in tissue PGE₂ levels (F(4,25)=4.235; p=0.009; η²=0.404), with diclofenac showing significantly lower values compared to the negative control and ketoprofen groups, while no significant differences were found for IL-17 or STAT3.

Conclusion: Topical NSAIDs demonstrated selective anti-inflammatory effects, primarily through significant suppression of tissue PGE₂, confirming effective local COX pathway inhibition. The absence of significant changes in IL-17 and STAT3 suggests that short-term topical therapy mainly targets prostaglandin-mediated inflammation rather than upstream cytokine or transcriptional pathways involved in rheumatoid arthritis pathogenesis, warranting further investigation into their long-term therapeutic benefits.

Keywords: arthritis, IL-17, NSAID, PGE2, STAT3