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Abstract Resveratrol (RSV) is a polyphenolic compound with potent anti-inflammatory and anti-oxidant properties. Although, RSV exhibited a therapeutic role in the experimental models of arthritis, its low bioavailability is considered a major obstacle. Piperine (PIP), an alkaloid, has been widely used as an effective bio-enhancer with drugs associated with low bioavailability. In addition, low dose radiation has been considered as an effective treatment for rheumatoid arthritis (RA). Aim: The current study was designed in order to explore the possible modulatory effects of combining RSV with PIP or low dose gamma (Þ)-radiation in adjuvant-induced arthritis in rats. Methods: In the adjuvant-induced arthritis model, rats were immunized at day 0 by sub-plantar injection of Freund’s complete adjuvant. RSV (50 mg/kg) and PIP (20 mg/kg) were orally administered concurrently once daily from day 14 for two weeks. Rats were exposed to low dose Þ-radiation at a total dose level of 0.5 Gy (2 x 0.25) at days 14 and 21. A standard anti-inflammatory drug, diclofenac (3mg/kg), was employed for treatment validation. The paw volume was measured every 4 days. On day 29, rats were sacrificed and serum levels of tumor necrosis factor-alpha (TNF-Ü), interleukin-1beta (IL-1Ý), thiobarbituric acid reactive substances (TBARS), and total nitrate/nitrite (NOx) were estimated. Ankles were dissected for histopathological examinations and immuno-histochemical estimation of nuclear factor-kappa B p65 (NF-mB p65) |