Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats

• Published in: European journal of pharmacology 2015-10, Vol.765, p.307-315
• Main Authors: Fahmy Wahba, Mariam Gamal, Shehata Messiha, Basim Anwar, Abo-Saif, Ali Ahmed
• Format: Article
• Language: English
• Subjects: Animals; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis, Experimental - drug therapy; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Biomarkers - blood; Cartilage Oligomeric Matrix Protein - blood; Dexamethasone; Female; Haloperidol; Haloperidol - administration & dosage; Haloperidol - pharmacology; Haloperidol - therapeutic use; Interleukin-10 - blood; Matrix Metalloproteinase 3 - blood; Methotrexate; Ramipril; Ramipril - administration & dosage; Ramipril - pharmacology; Ramipril - therapeutic use; Rat; Rats; Rheumatoid arthritis; Rheumatoid Factor - blood; Tumor Necrosis Factor-alpha - blood
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2015.08.026

Rheumatoid arthritis (RA) is a challenging autoimmune disorder, whose treatments usually cause severe gastrointestinal, renal and other complications. We aimed to evaluate the beneficial anti-arthritic effects of an angiotensin converting enzyme (ACE) inhibitor, ramipril and a dopamine receptor blocker, haloperidol, on Complete Freund's Adjuvant-induced RA in adult female albino rats. Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5mg/kg/day) and methotrexate (1mg/kg/day), and two treatment groups receiving ramipril (0.9mg/kg/day) and haloperidol (1mg/kg/day). Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein as specific rheumatoid biomarkers, serum immunoglobulin G and antinuclear antibody as immunological biomarkers, serum tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) as immunomodulatory cytokines, serum myeloperoxidase and C-reactive protein as inflammatory biomarkers, as well as malondialdehyde and glutathione reduced (GSH) as oxidative stress biomarkers were assessed. A histopathological study on joints and spleens was performed to support the results of biochemical estimations. Ramipril administration significantly corrected all the measured biomarkers, being restored back to normal levels except for MMP-3, TNF-α and IL-10. Haloperidol administration restored all the measured biomarkers back to normal levels except for TNF-α, IL-10 and GSH. In conclusion, ACE inhibitors represented by ramipril and dopamine receptor blockers represented by haloperidol may represent new promising protective strategies against RA, at least owing to their immunomodulatory, anti-inflammatory and antioxidant potentials.