Investigation on Effect of Combination Therapy of Fluoxetine and Dexamethasone in Experimental Models of Rheumatoid Arthritis

Abstract

Objective: The present study is aimed to investigate the effect of combination therapy of fluoxetine and dexamethasone for the treatment of rheumatoid arthritis in experimental models- adjuvant arthritis and methylated bovine serum albumin (antigen) induced arthritis. Materials and methods: Adjuvant arthritis was induced by injecting complete freund’s adjuvant on the subplantar surface in the left hind paw on day 0. Drug treatments of fluoxetine 2 mg/kg and/or dexamethasone (0.3, 0.1 or 0.05 mg/kg) were given from day 1 to day 21 daily. On day 5, arthritic index, paw oedema and C-reactive protein are measured. On day 21, rats were sacrificed and various parameters like Rheumatoid Factor, arthritic index, paw oedema, splenomegaly, erythrocyte sedimentation rate (ESR), oxidative stress markers of synovial tissue and histopathological evaluations of ankle joint were performed. In another set of experiments, in antigen induced arthritis, rats were immunized 14 days prior to induction of arthritis with 2 mg methylated bovine serum albumin suspended in freund’s adjuvant: saline (1:1) subcutaneously. Animals were treated with the fluoxetine 2mg /kg and/or dexamethasone 0.1 mg/kg from day 0 to day 7. On day 7, various parameters like joint diameter, WBC count, ESR and oxidative stress markers of synovial tissue were estimated and histopathological evalution of knee joint was performed. Results: In adjuvant arthritis, combination therapy with 0.3 mg/kg dexamethasone suppressed rheumatoid factor as well as splenomegaly and improved antioxidant assessments and histopathological changes significantly compared to dexamethasone 0.3 mg/kg treatment but showed aggrevation of stomach ulcers and weight loss. Combination group having 0.1 mg/kg dexamethasone also produced similar effect on C-reactive protein, arthritic index, paw oedema, antioxidant assessments, serum rheumatoid factor and histopathological evaluations. Fluoxetine treated group showed reduction only in splenomegaly and primary lesions. In antigen induced arthritis, combination group with 0.1 mg/kg dexamethasone significantly suppressed antioxidant assessments, ESR andhistopathological menifestations compared to dexamethasone 0.1 mg/kg while effects on WBC count and joint diameter were found similar. Conclusion: Combination therapy of fluoxetine and dexamethasone are more effective in experimental models of adjuvant induced arthritis and antigen induced arthritis.