International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2020.33.46AnissNadia Noble-Daoud ZaazaaAsmaa Magdy SalehMohamed Rabie Abdalla 12020161Background and Objective: Rheumatoid arthritis (RA) is the commonest form of chronic inflammatory autoimmune disease with unknown etiology that attacks joint tissue for unknown reasons and is influenced by genetic as well as environmental factors. The present study was aimed to investigate the anti-rheumatic effect of platelets rich plasma (PRP) and intra gel hyaluronic acid (HA) on complete freund's adjuvant (CFA) induced RA. Materials and Methods: A total of 32 adult male rats were categorized into 4 groups (n = 8): Normal control received vehicles only, RA group received CFA (0.1 mL) injected in the right hind paw, PRP group (50 μL) intra-articularly injected into the right inflamed knee and paw and HA group (50 μL) of HA sodium salt into the inflamed joints. All treatments were administered for 4 weeks. Serum MDA, GSH and GPx levels were investigated using ELISA as oxidative stress biomarkers. Serum CRP, IL-1β, TNF-α, COX-2, ALOX5, MMP-9 and LT-C4 were also determined using ELISA as inflammatory biomarkers. Specific rheumatoid marker COMP and MMP-3 expression levels were detected using qRT-PCR. Histopathological changes in the joint tissues were examined using hematoxylin and eosin (H and E) stain. X-ray was also performed in examining the bone and joints. Results: PRP and HA significantly reduced serum MDA and increased GSH and GPx levels. Tested drugs also significantly reduced CRP, IL-1β, TNF-α, COX-2, ALOX5, MMP-9 and LTC4 serum levels. Administration of PRP or HA normalized COMP and MMP-3 expression levels in CFA-induced RA rats. Histopathological analysis and X-ray of PRP or HA groups showed a gradual reduction in joint damage and cartilage erosion. 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