Protective Effects of Simvastatin and Hesperidin against Complete Freund's Adjuvant-Induced Rheumatoid Arthritis in Rats.
OBJECTIVE
Rheumatoid arthritis (RA) is a disabling autoimmune disease for which most current treatments cause massive complications, thereby limiting treatment dose and duration. The anti-arthritic effects of the 3-hydroxy-3-metylglutary-CoA reductase inhibitor, simvastatin, and the natural flavonoid, hesperidin, were investigated against complete Freund's adjuvant-induced RA in rats.


METHODS
A normal control group, an arthritis control group, 2 reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and 2 treatment groups receiving simvastatin (0.5 mg/kg/day) and hesperidin (200 mg/kg/day) were included in the study. Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein (COMP) as specific rheumatoid biomarkers, serum immunoglobulin G (IgG) and antinuclear antibody (ANA) as immunological biomarkers, serum tumor necrosis factor-alpha and interleukin-10 as immunomodulatory cytokines, serum myeloperoxidase (MPO) and C-reactive protein as inflammatory biomarkers, and malondialdehyde (MDA) and glutathione (GSH) as oxidative stress biomarkers were assessed, supported by joint and spleen histopathological study.


RESULTS
Simvastatin significantly improved all the measured biomarkers, with MMP-3, COMP, and GSH restored to normal levels. Hesperidin significantly improved all the measured biomarkers, with COMP, IgG, ANA, MPO, MDA and GSH restored to normal levels.


CONCLUSIONS
Simvastatin and hesperidin may be promising protective agents against RA through immunomodulatory, anti-inflammatory and antioxidant potentials.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt.
Yasmin Moustafa
YM
Ahmed
Basim A S
BA
Messiha
Ali Ahmed
AA
Abo-Saif
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology*; D006569:Hesperidin / Q000008:administration & dosage / Q000627:therapeutic use*; D007136:Immunoglobulins / Q000097:blood; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D018501:Antirheumatic Agents; D015415:Biomarkers; D007136:Immunoglobulins; D005620:Freund's Adjuvant; D019821:Simvastatin; D006569:Hesperidin