Chondroprotective and anti-inflammatory effects of S-methylisothiourea, an inducible nitric oxide synthase inhibitor in cartilage and synovial explants model of osteoarthritis

Venkanna Balaganur, Nitya Nand Pathak, Madhu Cholenahalli Lingaraju, Amar Sunil More, Najeeb Latief, Rashmi Rekha Kumari, Dinesh Kumar, Surendra K. Tandan

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Objectives To study the chondroprotective and anti-inflammatory potential of inducible nitric oxide synthase (iNOS) inhibitor S-methylisothiourea (SMT) in in-vitro model. Methods Rabbit cartilage explants were stimulated with recombinant human interleukin 1β (rhIL-1β), and the chondroprotective and anti-inflammatory effects of SMT were investigated. Rat synovial explants were stimulated with LPS, and the anti-inflammatory effect of SMT on synovium was studied. To examine the role of SMT in synovial inflammation mediated cartilage damage, LPS stimulated synovial explants were cultured with dead cartilage with or without SMT for 72 h. The culture medium was analysed for sulfated glycosaminoglycans (GAGs) and hydroxyproline as measure of proteoglycans and collagen degradation, respectively. Key findings SMT significantly reduced GAGs, hydroxyproline, matrix metalloproteinase (MMP)-13, tumour necrosis factor alpha (TNF-α), prostaglindin E2 (PGE2) and nitrite release in stimulated rabbit cartilage media indicating chondroprotective and anti-inflammatory effects of SMT in osteoarthritis (OA). Stimulated synovial explants caused release of nitrite, PGE2, IL-1β and TNF-α in the medium which were significantly reduced by SMT indicating its anti-inflammatory action. SMT significantly reduced GAGs and hydroxyproline in medium and shown protective effect against synovium-mediated cartilage damage. Conclusions SMT inhibited cartilage degradation, synovial inflammation and synovium-mediated cartilage damage, suggesting that SMT may be an agent for pharmacological intervention in OA.

Original languageEnglish (US)
Pages (from-to)1021-1031
Number of pages11
JournalJournal of Pharmacy and Pharmacology
Volume66
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • S-methylisothiourea
  • cartilage explants
  • osteoarthritis
  • synovial explants

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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