Mitigation of inflammation and oxidative stress in FCA-induced arthritic rat model through gum acacia intervention: a comprehensive in‑vivo study

Abstract

Rheumatoid arthritis is a persistent immune-mediated inflammatory disorder that primarily affects joint bones, impacting approximately 0.5-1.0% of the global population. People with RA are 1.5 times more likely to develop cardiovascular conditions, including atherosclerosis. This study explored the therapeutic potential of GAc in a rat model of RA induced by CFA, focusing on its impact on biomarkers associated with atherosclerosis. Molecular docking studies indicated strong binding affinities of GAc with key inflammatory cytokines, including TNF-α, IL-6, IL-1β, NF-κB and PRMT-1. The experimental model of 23 days involved the induction of arthritis by injecting 0.15 mL of CFA into the sub-plantar region of the rats' left hind paws. GAc was dissolved in distilled water and administered to rats via oral gavage. Our results revealed that the administration of GAc, particularly in combination with MtxSt (GAc 10 g/kg + MtxSt), significantly (p < 0.001) reduced arthritic scores, joint stiffness scores, paw thickness, levels of lipids (LDL, VLDL, TG, and TC), asymmetric dimethylarginine (ADMA), homocysteine, oxidative stress, and pro-inflammatory cytokines. In addition, GAc markedly (p < 0.001) improved body weight, hematological parameters (RBC, %HCT and Hb), HDL, dimethylarginine dimethylaminohydrolase-1(DDAH-1), and CST levels. Histopathological assessments showed that GAc 10 g/kg + MtxSt significantly alleviated bone and cartilage erosion (p < 0.001), pannus formation (p < 0.001), synovial hyperplasia (p < 0.01), vascular congestion (p < 0.001) and inflammatory cell infiltration (p < 0.001). The therapeutic efficacy of GAc is ascribed to its anti-inflammatory, antioxidant, and anti-atherosclerotic properties. This study suggested that combining GAc with MtxSt exerts a synergistic effect in mitigating inflammation and reducing the risk of atherosclerosis associated with RA.

Keywords: ADMA; Atherosclerosis; Gum acacia; Homocysteine; Methotrexate; Oxidative stress; Pro-inflammatory cytokines; Rheumatoid arthritis.