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

Pharm Biol. 2016 Sep;54(9):1705-15. doi: 10.3109/13880209.2015.1125931. Epub 2015 Dec 24.

Abstract

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.

Keywords: Anti-inflammatory; antioxidant; complete Freund’s adjuvant; dexamethasone; immuno-modulatory; methotrexate.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • 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
  • Cytokines / blood
  • Dexamethasone / pharmacology
  • Female
  • Fenofibrate / pharmacology*
  • Freund's Adjuvant
  • Immunosuppressive Agents / isolation & purification
  • Immunosuppressive Agents / pharmacology*
  • Inflammation Mediators / blood
  • Joints / drug effects
  • Joints / metabolism
  • Joints / pathology
  • Methotrexate / pharmacology
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Resveratrol
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology
  • Stilbenes / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Antirheumatic Agents
  • Biomarkers
  • Cytokines
  • Immunosuppressive Agents
  • Inflammation Mediators
  • Stilbenes
  • Dexamethasone
  • Freund's Adjuvant
  • Resveratrol
  • Fenofibrate
  • Methotrexate