Abstract

IMMUNOREGULATORY AND ANTI-INFLAMMATORY PROPERTIES OF PPAR-A RECEPTORS AND THEIR ENDOGENOUS AND EXOGENOUS LIGANDS IN ARTHROPATHIES: A SYSTEMATIC REVIEW

Ana Carolina Rocha de Melo Leite, William de Sousa Lira, Lílian Karla de Nojosa Rodrigues, Tsuleny de Souza Lima, Wladimir Lima de Melo Júnior, Deiziane Viana da Silva Costa, Francisco Airton Catro da Rocha and Rodolfo de Melo Nunes*

ABSTRACT

Arthropathies are associated with changes in lipid levels, which increase the risk of cardiovascular diseases. Therefore, peroxisome proliferator-activated receptor alpha (PPAR-α) agonists have emerged as an important tool in the prevention of cardiovascular diseases in rheumatic diseases by promoting the reduction of serum triglycerides and LDL, and elevation of plasma high-density lipoproteins. However, the effect of PPAR-α agonists may not be limited to dyslipidemia control alone and prevent the risk of cardiovascular diseases but also extend immunoregulatory effects in arthropathies. Therefore, we aimed to review the activity of PPAR-α ligands in arthritis in vivo and in vitro. This study conducted from 2010 to 2020, MEDLINE-PubMed, Science Direct, and Google Scholar were searched up to 30 December 2020. Of the 3490 publications initially selected, 22 that fit all the inclusion criteria were finally analysed. In experimental models, PPAR-α agonists showed anti-inflammatory, analgesic, chondroprotective, and antioxidant effects in arthritis. In vitro, PPAR-α agonists reversed the effects of inflammatory cytokines on fibroblasts, macrophages, chondrocytes, and osteoblasts, as well as the actions of growth factors on chondrocytes and bone cells. In clinical studies, fibrates reduced pain and disease activity scores and improved joint physical function in rheumatoid arthritis and osteoarthritis. In conclusion, the administration of PPAR-α agonists has immunoregulatory and anti-inflammatory effects in arthritis.

Keywords: PPAR-? agonists, models, rheumatic diseases, systematic review.