Protective effects of fenofibrate and resveratrol in an aggressive model of rheumatoid arthritis in rats

• Published in: Pharmaceutical biology 2016-09, Vol.54 (9), p.1705-1715
• Main Authors: Wahba, Mariam G. F., Messiha, Basim A. S., Abo-Saif, Ali A.
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; antioxidant; Antioxidants - isolation & purification; Antioxidants - pharmacology; Antirheumatic Agents - isolation & purification; Antirheumatic Agents - pharmacology; Arthritis, Experimental - blood; Arthritis, Experimental - chemically induced; Arthritis, Experimental - immunology; Arthritis, Experimental - prevention & control; Biomarkers - blood; complete Freund's adjuvant; Cytokines - blood; dexamethasone; Dexamethasone - pharmacology; Female; Fenofibrate - pharmacology; Freund's Adjuvant; immuno-modulatory; Immunosuppressive Agents - isolation & purification; Immunosuppressive Agents - pharmacology; Inflammation Mediators - blood; Joints - drug effects; Joints - metabolism; Joints - pathology; methotrexate; Methotrexate - pharmacology; Oxidative Stress - drug effects; Rats, Wistar; Spleen - drug effects; Spleen - metabolism; Spleen - pathology; Stilbenes - pharmacology
• ISSN: 1388-0209; 1744-5116
• DOI: 10.3109/13880209.2015.1125931

Context Fibrates were reported to have anti-inflammatory effects while the naturally occurring polyphenol resveratrol was traditionally known as a potent antioxidant agent. Objective The effects of fenofibrate and resveratrol were investigated on complete Freund's adjuvant (CFA)-induced rheumatoid arthritis (RA) in adult female albino rats. Materials and methods Rats were divided into a normal control group, an arthritis control group receiving CFA, two reference treatment groups receiving dexamesathone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving fenofibrate (100 mg/kg/day) and resveratrol (10 mg/kg/day) for seven consecutive days. Assessment of RA was performed by measuring serum rheumatoid factor (RF), matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein (COMP) as specific rheumatoid biomarkers, immunoglobulin G (IgG) and antinuclear antibody (ANA) as immunological biomarkers, tumour necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) as immunomodulatory cytokines, myeloperoxidase (MPO) and C-reactive protein (CRP) as inflammatory biomarkers and malondialdehyde (MDA) and glutathione (GSH) as oxidative stress biomarkers, supported by a histopathological study on joints and spleens. Results Serum RF, MMP-3, COMP, IgG, ANA, TNF-α, MPO, CRP and MDA were decreased to about 36, 56, 66, 65, 9, 35, 24, 44 and 31% by fenofibrate, and to about 37, 59, 44, 70, 5, 30, 23, 33 and 28% by resveratrol treatments, respectively. Alternatively, serum IL-10 and GSH were significantly increased to about 215 and 251% by fenofibrate and to about 225 and 273% by resveratrol treatments, respectively. Discussion and conclusion Fenofibrate and resveratrol protect against RA, possibly through their immunomodulatory, anti-inflammatory and antioxidant potential.