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


RESULTS
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.
Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Bareilly, UP, India.
Venkanna
V
Balaganur
Nitya Nand
NN
Pathak
Madhu Cholenahalli
MC
Lingaraju
Amar Sunil
AS
More
Najeeb
N
Latief
Rashmi Rekha
RR
Kumari
Dinesh
D
Kumar
Surendra K
SK
Tandan
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008070:Lipopolysaccharides; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004791:Enzyme Inhibitors; D006025:Glycosaminoglycans; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009573:Nitrites; D007550:Isothiuronium; D052247:Nitric Oxide Synthase Type II; D053509:Matrix Metalloproteinase 13; C027744:S-methylisothiopseudouronium; D006909:Hydroxyproline
S-methylisothiourea; cartilage explants; osteoarthritis; synovial explants