Possible Protective Effect of Trimetazidine Alone and in Combination with Methotrexate in Attenuating Joint Inflammation in Freund’s Adjuvants Induced Rheumatoid Arthritis in Rats

Abstract

Abstract Rheumatoid Arthritis is a complex chronic auto-immune systemic illness. It is primarily characterized by synovial hyperplasia and localized pro-inflammatory cytokine production that causes chronic synovitis and a long-lasting inflammation of the joints and bones. The study's goal was to look into the potential anti-arthritic effects of trimetazidine in a rat model of Freund’s complete adjuvant (FCA)-induced arthritis, which has many clinical and biochemical similarities to rheumatoid arthritis (RA). The underlying antirheumatoid arthritis mechanism, as well as its impact on TLR4/NFKB pathway were investigated to understand and confirm its potential efficacy in RA treatment. Our study was based on 4 groups, control group received saline injections, trimetazidine (7.2 mg/kg/day) treated group, methotrexate (0.75 mg/kg/week) treated group and combination group that received both medications in the same doses for 21 days. The degree of ipsilateral paw swelling, ankle diameter, body weight, tissue expression levels of TLR4(toll like receptor) and NFKB (nuclear factor kappa b) in paw, and serum ACPA (anticitrullinated protein antibodies) were all measured. With a slight but not statistically significant impact on ankle diameter, trimetazidine and methotrexate considerably reduced the arthritic symptoms as indicated by ipsilateral paw volume. It had no discernible impact on body weight. Together with the overall improved synovial hyperplasia and cartilage disarrangements, TLR4 and NFKB expression in synovial tissue were reduced. In a rat model of CFA-induced arthritis, trimetazidine displays a considerable anti- inflammatory impact that is even better than methotrexate and has the potential to be anti-arthritic. Additionally, there is a large additive effect between the two medications.