POTENTIATION OF THE ANTI-INFLAMMATORY ACTIVITY OF NIMESULIDE AND KETOROLAC BY CELL-FREE CRYOPRESERVED BIOLOGICAL PRODUCTS IN EXPERIMENTAL RHEUMATOID ARTHRITIS

Abstract

Introduction. Rheumatoid arthritis remains one of the leading causes of chronic pain, progressive joint dysfunction, and reduced quality of life. A promising strategy involves biotechnological potentiation of the therapeutic effects of nonsteroidal anti-inflammatory drugs using cell-free cryopreserved biological products, particularly placental cryoextract and conditioned medium derived from mesenchymal stromal cells. The Aim of the Study – to evaluate the effect of placental cryoextract and mesenchymal stromal cell conditioned medium on the anti-inflammatory efficacy of nimesulide and ketorolac under conditions of experimental rheumatoid arthritis in rats, based on hematological and biochemical parameters. Research Methods. Adjuvant arthritis was induced in rats by administration of complete Freund’s adjuvant. The study involved forty-two male rats randomized into six groups. Treatment was administered from day 14 to day 28: nimesulide and ketorolac were given intragastrically, while placental cryoextract and mesenchymal stromal cell conditioned medium were administered intramuscularly every two days. On day 28, leukocyte count, erythrocyte sedimentation rate, and C-reactive protein concentration were determined. Results and Discussion. In the untreated control group, a pronounced systemic inflammatory response developed, characterized by leukocytosis exceeding 21×109/L, an almost fourfold increase in the erythrocyte sedimentation rate, and an elevation of C-reactive protein to 19.0 mg/L. Nimesulide monotherapy reduced leukocyte counts to 13.1×109/L, decreased the erythrocyte sedimentation rate to 12.0 mm/h, and lowered C-reactive protein levels to 14.0 mg/L; however, these parameters remained higher than those observed in intact animals. The combination of nimesulide with placental cryoextract resulted in a more pronounced normalization, with leukocyte counts decreasing to 8.3×109/L, erythrocyte sedimentation rate to 6.0 mm/h, and C-reactive protein to 9.6 mg/L. Ketorolac monotherapy demonstrated a limited effect, whereas its combination with mesenchymal stromal cell conditioned medium showed the greatest efficacy, approaching intact values for leukocyte counts and erythrocyte sedimentation rate and reducing C-reactive protein levels to 11.9 mg/L. Conclusions. Under conditions of adjuvant-induced arthritis in rats, it was established that monotherapy with nimesulide and ketorolac provides only partial reduction of systemic inflammatory response parameters. The addition of placental cryoextract to nimesulide and mesenchymal stromal cell conditioned medium to ketorolac was associated with a more pronounced decrease in leukocytosis, a reduction in erythrocyte sedimentation rate, and a decrease in C-reactive protein levels compared with NSAID monotherapy. The obtained results indicate that cell-free cryopreserved biological products potentiate the anti-inflammatory efficacy of nimesulide and ketorolac under experimental arthritis conditions.