Concerted regulation of OPG/RANKL/NF-κB/MMP-13 trajectories contribute to ameliorative capability of prodigiosin and/or low dose γ-radiation against adjuvant- induced arthritis in rats

Background: Prodigiosin (PDG) is a microbial red dye with antioxidant and anti-inflammatory properties, although its effect on rheumatoid arthritis (RA) remains uncertain. Also, multiple doses of low dose gamma- radiation (LDR) have been observed to be as a successful intervention for RA. Thus, the purpose of this study was to investigate the ameliorative potential of PDG and/or LDR on adjuvant-induced arthritis (AIA) in rats. Methods: The anti-inflammatory and anti-arthritic effects of PDG and/or LDR were examined in vitro and in vivo, respectively. In the AIA model, the arthritic indexes, paw swelling degrees, body weight gain, and histopatho-logical assessment in AIA rats were assayed. The impact of PDG (200 mu g/kg; p.o) and/or LDR (0.5 Gy) on the levels of pro-and anti-inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IL-18, IL-17A, and IL-10) as well as the regulation of osteoprotegrin (OPG)/ receptor activator of nuclear factor kappa B ligand (RANKL)/ nuclear factor-kappa B (NF-kappa B)/MMP-13 pathways was determined. Methotrexate (MTX; 0.05 mg/kg; twice/week, i.p) was adminis-tered concurrently as a standard anti-arthritic drug. Results: PDG and/or LDR markedly diminished the arthritic indexes, paw edema, weigh loss in AIA rats, alleviated the pathological alterations in joints, reduced the levels of pro-inflammatory cytokines IL-1 beta, TNF-alpha, IL-6, IL-18, IL-17A, and RANKL in serum and synovial tissues, while increasing anti-inflammatory cytokines IL-10 and OPG levels. Moreover, PDG and/or LDR down-regulated the expression of RANKL, NF-kappa Bp65, MMP13, caspase-3, and decreased the RANKL/OPG ratio, whereas OPG and collagen II were enhanced in synovial tissues.Conclusion: PDG and/or LDR exhibited obvious anti-RA activity on AIA.