Sulforaphane Modulates Joint Inflammation in a Murine Model of Complete Freund's Adjuvant-Induced Mono-Arthritis

Molecules. 2018 Apr 24;23(5):988. doi: 10.3390/molecules23050988.

Abstract

Rheumatoid arthritis (RA) is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN) is a natural compound that has been suggested as an antioxidant. Here, SFN’s effects were evaluated in a murine mono-arthritis model. Mono-arthritis was induced in mice by a single intra-articular injection of Complete Freund’s Adjuvant (CFA-10 µg/joint, in 10 µL) into the ipsilateral joint. The contralateral joint received an equal volume of PBS. On the 4th day post-joint inflammation induction, animals received either SFN (10 mg/kg) or vehicle (3% DMSO in saline), intraperitoneally (i.p.), twice a day for 3 days. Joint swelling and secondary mechanical allodynia and hyperalgesia were evaluated over 7 days post-CFA. After this period, animals were culled and their blood and synovial fluid samples were collected for analysis of cell populations, cytokine release and thioredoxin reductase (TrxR) activity. Knee joint samples were also collected for histology. SFN reduced joint swelling and damage whilst increasing the recruitment of Ly6C⁺ and Ly6G⁺ cells to CFA-injected joints. SFN-treated animals presented down-regulation of CD11b and CD62L on synovial fluid Ly6G⁺ cells. Synovial fluid samples obtained from CFA-injected joints and plasma samples of SFN-treated mice presented higher levels of IL-6 and increased activity of TrxR, in comparison with controls. These results indicate that SFN reduces knee joint damage by modulating cell activation/migration to the joints, cytokine production and increasing the activity of TrxR, and therefore, may represent an alternative treatment to joint inflammation.

Keywords: IL-6; oedema; rheumatoid arthritis; sulforaphane; thioredoxin reductase.

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / etiology*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Biomarkers
  • Cytokines / metabolism
  • Disease Models, Animal
  • Freund's Adjuvant / adverse effects*
  • Histocytochemistry
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation Mediators
  • Isothiocyanates / pharmacology*
  • Knee Joint / drug effects
  • Knee Joint / metabolism
  • Knee Joint / pathology
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Mice
  • Phenotype

Substances

  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Isothiocyanates
  • Freund's Adjuvant
  • sulforaphane