A PRECLINICAL STUDY FOCUSSING ON OXIDATIVE STRESS IN ADJUVANT ARTHRITIS RAT MODEL TO EVALUATE THE EFFECT OF VARIOUS MOLECULAR WEIGHTS OF HYALURONIC ACID IN MONOTHERAPY AND IN COMBINATION WITH METHOTREXATE

Background: Hyaluronic acid (HA) has been shown in recent research to have chondroprotective and anti-inflammatory effects in rheumatoid arthritis. Objectives: The purpose of this study was to examine HA and its combination with methotrexate (MTX) in rats suffering from adjuvant arthritis (AA). Methods: In our studies, we used male Lewis rats and the arthritis was induced by intradermal injection of 0.1 mL suspension of heat-killed Mycobacterium butyricum mixed with incomplete Freund’s adjuvants at a dosage of 12 mg/mL into the base of a tail of Lewis rats (1,2). These groups of animals were included in the experiment: healthy controls, animals with arthritis who were not treated, animals with arthritis who received treatment with HA and MTX, and animals with arthritis who received treatment with HA and MTX combined. Animals received daily doses of 0.5 mg and 5 mg/kg b.w. of HA of varying molecular weights (0.43, 0.99, and 1.73 MDa) alone or combined with methotrexate in an oral dose of 0.3 mg/kg b.w. twice weekly. Results: We measured improving effect of HA on antioxidant enzymes in erythrocytes (superoxide dismutase and glutathione peroxidase) and on plasma antioxidant capacity. Further, we discovered that HA decreased the amount of lipid hydroperoxides in plasma, a sign of oxidative damage to lipids developing during arthritis. The effect of HA with the highest molecular weight was the most notable not only on the oxidative stress parameters, but also on inflammatory markers and the main biometric markers. Conclusion: HA and MTX therapy together prevented the development of arthritis in rats more successfully than MTX alone. There is a possibility that this finding will lead to improved treatments for rheumatoid arthritis patients after its clinical implementation. REFERENCES: [1] Bauerova, Katarina, et al.. The role of endogenous antioxidants in the treatment of experimental arthritis. In Antioxidants 2019 Apr 6. IntechOpen [2] Chrastina, Martin - Drafi, František - Pružinska, Katarina - Poništ, Silvester - Kamga, Kevine Silihe - Khademnematolahi, Sasan et al 2023. Crocus sativus L. Extract (Saffron) Effectively Reduces Arthritic and Inflammatory Parameters in Monotherapy and in Combination with Methotrexate in Adjuvant Arthritis. Nutrients 15(2023): 4108. Table 1. Acknowledgements: Projects APVV-15-0308 and VEGA 2/0136/20. Czech company Contipro has deliver all hyaluronic compounds for this experiment. Disclosure of Interests: None declared. DOI: 10.1136/annrheumdis-2024-eular.5219 Keywords: Biomarkers, Animal Models, Cytokines and Chemokines Citation: , volume 83, supplement 1, year 2024, page 1684Session: Rheumatoid arthritis (Publication Only)

Biomarkers, Animal Models, Cytokines and Chemokines