Leflunomide with Meloxicam on Progression of Rheumatoid Arthritis and its Associated Depression in AIA Rats

Abstract

Background: Rheumatoid arthritis is an autoimmune disorder in which patients not only suffer from joint misery but also face its associated depression. Objectives: To evaluate the anti-arthritic effects of leflunomide (5 mg.kg-1.day-1) and meloxicam (5 mg.kg-1.day-1) when given together on progression of rheumatoid arthritis and its associated depression in Adjuvant-Induced Arthritic (AIA) rats. Methodology: AIA was induced in female Sprague-Dawley rats. Paw volumes was measured to evaluate arthritic progression while brain indolamines (tryptophan, serotonin and its metabolite 5-hydroxyindoleacetic acid) were estimated by HPLC-EC method to determine associated depression. Leflunomide and meloxicam were given orally and intraperitoneally throughout the experiment. Results: Leflunomide and meloxicam inhibited RA progression significantly (p<0.005), in terms of joint erythema and limb swelling, when given alone but fail to do so in combination in contrast to untreated or saline-treated arthritic rats. Significant reduction (p<0.005) in all brain indolamines levels was found in all arthritic rats when compared with normal. Furthermore, treatment with leflunomide and meloxicam alone or mutually significantly decrease (p<0.005) brain indolamines level in comparison with untreated or saline-treated arthritic rats. Conclusion: Leflunomide and meloxicam though reduces RA progression when given alone but in combined therapy produce severe adverse effect. Depression is prominent with RA and therapy with leflunomide and meloxicam exaggerate the conditions.